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Background Meta-analyses of randomized controlled trials have suggested an increased long-term mortality risk following femoropopliteal and infrapopliteal angioplasty using paclitaxel-coated devices. This study was conducted to evaluate long-term mortality after paclitaxel drug-coated balloon (DCB) and plain old balloon angioplasty (POBA) of infrapopliteal lesions in real-world practice. Methods A retrospective mortality analysis of patients with at least 3 years of follow-up who underwent balloon-based endovascular therapy of infrapopliteal lesions was performed. Results Overall, 2,424 patients with infrapopliteal lesions were treated within the study period. Five hundred seventy-six patients fulfilled the study criteria. Of those, 269 patients were treated with uncoated devices without crossover to a paclitaxel-coated device during follow-up and 307 patients with DCB angioplasty. Mean (SD) follow-up was 46.48 (32.77) months. The mortality rate was 66.9% after POBA and 46.9% after DCB (P < .001). In the matched-pair cohort, 164 patients died after uncoated treatment (66.7%), and 119 in the DCB group died (48.4%; P < .001). There was no correlation between DCB length and mortality rate (P = .357). For the entire cohort, multivariate logistic regression analysis showed type of treatment (uncoated device vs DCB; P = .002), age (P < .001), stroke (P = .005), renal insufficiency (P = .014), and critical limb ischemia (P = .001) to be independent predictors of all-cause mortality. There was no significant difference in mortality among the paclitaxel exposure groups. Conclusion In this real-world retrospective analysis, the long-term mortality rate was lower after DCB angioplasty than after POBA of infrapopliteal lesions.

Background Abdominal aortic aneurysm (AAA) has risk factors similar to those of atherosclerosis. Salusin-β and arterial stiffness are novel parameters that have been shown to predict atherosclerosis and related cardiovascular disorders. However, their predictive value for detecting AAA remains unclear. Methods Forty-eight patients with AAA and 47 age- and sex-matched participants without AAA were enrolled in the study. Arterial stiffness parameters were obtained via an oscillometric Mobil-O-Graph PWA Monitor device (IEM GmbH) with integrated ARCSolver software (Australian Institute of Technology). Plasma salusin-β levels were analyzed using an enzyme-linked immunosorbent assay reagent kit (Abbkine, Inc). The measured salusin-β levels and arterial stiffness parameters of the AAA and control groups were compared. Results Salusin-β levels were significantly lower in patients with AAA (P = .014). There was a significant negative correlation between salusin-β levels and abdominal aorta diameter. No significant difference was detected between AAA and control groups in terms of arterial stiffness parameters (P > .05). In backward multiple regression analysis, the presence of AAA, platelet count, and augmentation index were found to be independent predictors of salusin-β levels (P = .006 and P = .023, respectively). Conclusion Arterial stiffness parameters were not found to be associated with AAA. Contrary to previous results regarding atherosclerosis and related cardiovascular disorders, salusin-β levels were found to be lower in patients with AAA. Although AAA is thought to have similar risk factors as atherosclerosis, the exact pathophysiologic mechanism remains unclear.

Nanomedicine holds promise for the delivery of therapeutic and imaging agents to improve cancer treatment outcomes. Preclinical studies have demonstrated that high-density lipoprotein (HDL) nanoparticles accumulate in tumor tissue on intravenous administration. Whether this HDL-based nanomedicine concept is feasible in patients is unexplored. Using a multimodal imaging approach, we aimed to assess tumor uptake of exogenously administered HDL nanoparticles in patients with esophageal cancer. Methods: The HDL mimetic CER-001 was radiolabeled using (89)Zr to allow for PET/CT imaging. Patients with primary esophageal cancer staged T2 and above were recruited for serial (89)Zr-HDL PET/CT imaging before starting chemoradiation therapy. In addition, patients underwent routine (18)F-FDG PET/CT and 3-T MRI scanning (diffusion-weighted imaging/intravoxel incoherent motion imaging and dynamic contrast-enhanced MRI) to assess tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability. Tumor biopsies were analyzed for the expression of HDL scavenger receptor class B1 and macrophage marker CD68 using immunofluorescence staining. Results: Nine patients with adenocarcinoma or squamous cell carcinoma underwent all study procedures. After injection of (89)Zr-HDL (39.2 ± 1.2 [mean ± SD] MBq), blood-pool SUV(mean) decreased over time (11.0 ± 1.7, 6.5 ± 0.6, and 3.3 ± 0.5 at 1, 24, and 72 h, respectively), whereas liver and spleen SUV(mean) remained relatively constant (4.1 ± 0.6, 4.0 ± 0.8, and 4.3 ± 0.8 at 1, 24, and 72 h, respectively, for the liver; 4.1 ± 0.3, 3.4 ± 0.3, and 3.1 ± 0.4 at 1, 24, and 72 h, respectively, for the spleen) and kidney SUV(mean) markedly increased over time (4.1 ± 0.9, 9.3 ± 1.4, and 9.6 ± 2.0 at 1, 24, and 72 h, respectively). Tumor uptake (SUV(peak)) increased over time (3.5 ± 1.1 and 5.5 ± 2.1 at 1 and 24 h, respectively [P = 0.016]; 5.7 ± 1.4 at 72 h [P = 0.001]). The effective dose of (89)Zr-HDL was 0.523 ± 0.040 mSv/MBq. No adverse events were observed after the administration of (89)Zr-HDL. PET/CT and 3-T MRI measures of tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability did not correlate with tumor uptake of (89)Zr-HDL, suggesting that a specific mechanism mediated the accumulation of (89)Zr-HDL. Immunofluorescence staining of clinical biopsies demonstrated scavenger receptor class B1 and CD68 positivity in tumor tissue, establishing a potential cellular mechanism of action. Conclusion: To our knowledge, this was the first (89)Zr-HDL study in human oncology. (89)Zr-HDL PET/CT imaging demonstrated that intravenously administered HDL nanoparticles accumulated in tumors of patients with esophageal cancer. The administration of (89)Zr-HDL was safe. These findings may support the development of HDL nanoparticles as a clinical delivery platform for drug agents. (89)Zr-HDL imaging may guide drug development and serve as a biomarker for individualized therapy.

Body surface potential mapping (BSPM) is a noninvasive modality to assess cardiac bioelectric activity with a rich history of practical applications for both research and clinical investigation. BSPM provides comprehensive acquisition of bioelectric signals across the entire thorax, allowing for more complex and extensive analysis than the standard electrocardiogram (ECG). Despite its advantages, BSPM is not a common clinical tool. BSPM does, however, serve as a valuable research tool and as an input for other modes of analysis such as electrocardiographic imaging and, more recently, machine learning and artificial intelligence. In this report, we examine contemporary uses of BSPM, and provide an assessment of its future prospects in both clinical and research environments. We assess the state of the art of BSPM implementations and explore modern applications of advanced modeling and statistical analysis of BSPM data. We predict that BSPM will continue to be a valuable research tool, and will find clinical utility at the intersection of computational modeling approaches and artificial intelligence.

Propolis is a complex natural product that possesses antioxidant, anti-inflammatory, immunomodulatory, antibacterial, and antiviral properties mainly attributed to the high content in flavonoids, phenolic acids, and their derivatives. The chemical composition of propolis is multifarious, as it depends on the botanical sources from which honeybees collect resins and exudates. Nevertheless, despite this variability propolis may have a general pharmacological value, and this review systematically compiles, for the first time, the existing preclinical and clinical evidence of propolis activities as an antiviral and immunomodulatory agent, focusing on the possible application in respiratory diseases. In vitro and in vivo assays have demonstrated propolis broad-spectrum effects on viral infectivity and replication, as well as the modulatory actions on cytokine production and immune cell activation as part of both innate and adaptive immune responses. Clinical trials confirmed propolis undeniable potential as an effective therapeutic agent; however, the lack of rigorous randomized clinical trials in the context of respiratory diseases is tangible. Since propolis is available as a dietary supplement, possible use for the prevention of respiratory diseases and their deleterious inflammatory drawbacks on the respiratory tract in humans is considered and discussed. This review opens up new perspectives on the clinical investigation of neglected propolis biological properties which, now more than ever, are particularly relevant with respect to the recent outbreaks of pandemic respiratory infections.

Identification of low-dose, low-molecular-weight, drug-like inhibitors of protein-protein interactions (PPIs) is a challenging area of research. Despite the challenges, the therapeutic potential of PPI inhibition has driven significant efforts toward this goal. Adding to recent success in this area, we describe herein our efforts to optimize a novel purine carboxylic acid-derived inhibitor of the HDM2-p53 PPI into a series of low-projected dose inhibitors with overall favorable pharmacokinetic and physical properties. Ultimately, a strategy focused on leveraging known binding hot spots coupled with biostructural information to guide the design of conformationally constrained analogs and a focus on efficiency metrics led to the discovery of MK-4688 (compound 56), a highly potent, selective, and low-molecular-weight inhibitor suitable for clinical investigation.

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. Methods: We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy. All patients underwent pretreatment whole-body 18F-FDG PET/CT. To quantify effects due to the tumor itself, the gross tumor volume (GTV) was directly contoured on the PET/CT image. Meanwhile, to quantify effects arising from the rest of the body, the planning target volume (PTV) was deformably registered from each planning CT to the PET/CT scan, and a semiautomated approach combining seed-growing and manual contour review generated whole-body muscle, bone, and fat segmentations on each PET/CT image. A total of 965 radiomic features were extracted for GTV, PTV, muscle, bone, and fat. Ninety-five patients were used to train a Cox model of disease recurrence including both radiomic and clinical features (age, stage, tumor grade, histology, and baseline complete blood cell counts), using bagging and split-sample-validation for feature reduction and model selection. To further avoid overfitting, the resulting models were tested for generalization on the remaining 32 patients, by calculating a risk score based on Cox regression and evaluating the c-index (c-index > 0.5 indicates predictive power). Results: Optimal performance was seen in a Cox model including 1 clinical biomarker (whether or not a tumor was stage III-IVA), 2 GTV radiomic biomarkers (PET gray-level size-zone matrix small area low gray level emphasis and zone entropy), 1 PTV radiomic biomarker (major axis length), and 1 whole-body radiomic biomarker (CT bone root mean square). In particular, stratification into high- and low-risk groups, based on the linear risk score from this Cox model, resulted in a hazard ratio of 0.019 (95% CI, 0.004, 0.082), an improvement over stratification based on clinical stage alone, which had a hazard ratio of 0.36 (95% CI, 0.16, 0.83). Conclusion: Incorporating nontumor radiomic biomarkers can improve the performance of prognostic models compared with using only clinical and tumor radiomic biomarkers. Future work should look to further test these models in larger, multiinstitutional cohorts.

Objectives Previous studies have found that severe acute respiratory syndrome (SARS) was associated with the physical and psychological stress of those infected. However, research is sparse regarding the long‐term health consequence of community SARS exposure for older adults. Methods Using data from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS), we estimated multilevel regression models of allostatic load (AL) in the years after the SARS epidemic among 7735 respondents. Interaction terms between SARS epidemic exposure and social participation or community environment were included to examine potential effects. Results We found that community SARS exposure was associated with greater AL for those who had no social participation. Among those who were in worse community environment, community SARS exposure was strongly related to elevated load in the cardiovascular system. However, for those had social participation and lived in better community environment, community SARS exposure manifested no association with AL years later. Active social participation and better community environment could offset the negative association between SARS exposure and AL. Conclusions Taken together, these findings helped determine the positive direction of future social efforts and policy decisions to guide the global recovery from the devastating COVID‐19 pandemic.

Patients on maintenance hemodialysis (MHD), which are at high risk of infection by SARS-CoV-2 virus and death due to COVID-19, have been prioritized for vaccination. However, because they were excluded from pivotal studies and have weakened immune responses, it is not known whether these patients are protected after the “standard” two doses of mRNA vaccines. To answer this, anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured in the circulation 10-14 days after the second injection of BNT162b2 vaccine in 106 patients receiving MHD (14 with history of COVID-19) and compared to 30 healthy volunteers (four with history of COVID-19). After vaccination, most (72/80, 90%) patients receiving MHD naïve for the virus generated at least one type of immune effector, but their response was weaker and less complete than that of healthy volunteers. In multivariate analysis, hemodialysis and immunosuppressive therapy were significantly associated with absence of both anti-RBD IgGs and anti-spike CD8+ T cells. In contrast, previous history of COVID-19 in patients receiving MHD correlated with the generation of both types of immune effectors anti-RBD IgG and anti-spike CD8+ T cells at levels similar to healthy volunteers. Patients receiving MHD naïve for SARS-Cov-2 generate mitigated immune responses after two doses of mRNA vaccine. Thus, the good response to vaccine of patients receiving MHD with a history of COVID-19 suggest that these patients may benefit from a third vaccine injection., Graphical abstract

Solid organ transplant recipients are at high risk for the development of severe forms of COVID-19. However, the role of immunosuppression in the morbidity and mortality of the immune phenotype during COVID-19 in transplant recipients remains unknown. In this retrospective study, we compared peripheral blood T and B cell functional and surface markers, as well as serum antibody development during 29 cases of mild (World Health Organization 9-point Ordinal Scale (WOS) of 3-4) and 22 cases of severe COVID-19 (WOS 5-8) in solid organ transplant (72% kidney transplant) recipients hospitalized in our center. Patients who developed severe forms of COVID-19 presented significantly lower CD3+ (median 344/mm3 (inter quartile range 197; 564) vs. 643/mm3 (397; 1251), and CD8+ T cell counts (124/mm3 (76; 229) vs. 240/mm3 (119; 435). However, activated CD4+ T cells were significantly more frequent in severe forms (2.9% (1.37; 5.72) vs. 1.4% (0.68; 2.35), counterbalanced by a significantly higher proportion of Tregs (3.9% (2.35; 5.87) vs 2.7% (1.9; 3.45)). A marked decrease in the proportion of NK cells was noted only in severe forms. In the B cell compartment, transitional B cells were significantly lower in severe forms (1.2% (0.7; 4.2) vs. 3.6% (2.1; 6.2). Nonetheless, a majority of transplant recipients developed antibodies against SARS-CoV-2 (77% and 83% in mild and severe forms respectively). Thus, our data revealed immunological differences between mild and severe forms of COVID 19 in solid organ transplant recipients, similar to previous reports in the immunocompetent population., Graphical abstract

Purpose: To determine the effectiveness of salvage radiation therapy (RT) in patients with locoregional recurrence (LRR) following initial curative resection of non-small cell lung cancer (NSCLC) and identify the prognostic factors affecting survival. Materials and Methods: Between January 2009 and January 2019, 54 patients with LRR after NSCLC surgery were treated with salvage RT (83.3%) or concurrent chemoradiation therapy (16.7%). Twenty-three (42.6%), 21 (38.9%), and 10 (18.5%) patients had local, regional, and both recurrences, respectively. The median RT dose was 66 Gy (range, 37.5 to 70 Gy). The radiation target volume included recurrent lesions with or without regional lymphatics depending on the location and recurrence type. Results: The median follow-up time from the start of RT was 28.3 months (range, 2.4 to 112.4 months) and disease-free interval (DFI) from surgery to recurrence was 21.0 months (range, 0.5 to 92.3 months). Tumor response after RT was complete response, partial response, stable disease, and progressive disease in 17, 29, 5, and 3 patients, respectively. The rates of freedom from local progression at 1 and 2 years were 77.2% and 66.0%, respectively. The median survival duration after RT was 24.8 months, and the 2-year overall survival (OS) rate was 51.1%. On univariate analysis, initial stage, recurrence site, DFI, and tumor response after RT were significant prognostic factors for OS. DFI ≥12 months and tumor response after RT were statistically significant factors on multivariate Cox analysis for OS. Conclusion: Our results demonstrated the effectiveness of salvage RT for LRR of NSCLC following curative surgery.

Purpose: Image-guided radiotherapy (IGRT) is central to the safe and effective delivery of ultrahypofractionated (UF) stereotactic body radiotherapy (SBRT) for localized prostate cancer. However, the optimal IGRT modality remains uncertain. We aim to study the safety of performing UF-SBRT using cone-beam computed tomography (CBCT) and real-time transperineal ultrasound (TPUS) monitoring. Materials and Methods: We retrospectively review the medical records of 26 patients who had received UF-SBRT for intermediate risk localized prostate cancer in our institution from October 2018 to December 2020. All patients were treated with SBRT without fiducial marker and received 35–40 Gy to the clinical target volume in 5 fractions over 2–5 weeks. CBCT was used to correct for interfraction displacement while intrafraction displacement of the prostate gland was monitored using Elekta Clarity Autoscan TPUS with 4 mm isotropic warning level. All patients also received neoadjuvant and concurrent androgen deprivation therapy for a total of 6 months. The primary endpoints were incidence of acute toxicities and patient reported urinary toxicities in terms of the International Prostate Symptom Score: before (IPSS1), at the completion of (IPSS2), and at 3–6 months (IPSS3) after SBRT. Results: All men were treated and followed up for at least 3 months after SBRT. Patients experienced transient worsening of their urinary symptoms at the end of SBRT but they usually recovered in 3–6 months afterwards. The median IPSS1, IPSS2, and IPSS3 were 12, 12.5, and 8, respectively. One patient developed grade 3 rectal bleeding which was related to underlying hemorrhoid. No other grade 3–4 acute toxicity was observed. Conclusion: It appears safe to deliver UF-SBRT without fiducial marker for prostate cancer patients using CBCT and non-invasive hybrid imaging modalities for positioning and tracking. Longer follow-up is necessary to monitor the treatment efficacy and long-term toxicities.

Purpose: To investigate the safety and efficacy of hypofractionated radiation therapy (HFRT) in patients with non-small cell lung cancer who are unfit for surgery or stereotactic body radiation therapy (SBRT) at our institution.Materials and Methods: From May 2007 to December 2018, HFRT was used to treat 68 lesions in 64 patients who were unsuitable for SBRT because of central tumor location, large tumor size, or contiguity with the chest wall. The HFRT schedule included a dose of 50–70 Gy delivered in 10 fractions over 2 weeks. The primary outcome was freedom from local progression (FFLP), and the secondary endpoints included overall survival (OS), disease-free survival, and toxicities.Results: The median follow-up period was 25.5 months (range, 5.3 to 119.9 months). The FFLP rates were 79.8% and 67.8% at 1 and 2 years, respectively. The OS rates were 82.8% and 64.1% at 1 and 2 years, respectively. A larger planning target volume was associated with lower FFLP (p = 0.023). Dose escalation was not associated with FFLP (p = 0.964). Four patients (6.3%) experienced grade 3–5 pulmonary toxicities. Tumor location, central or peripheral, was not associated with either grade 3 or higher toxicity.Conclusion: HFRT with 50–70 Gy in 10 fractions demonstrated acceptable toxicity; however, the local control rate can be improved compared with the results of SBRT. More studies are required in patients who are unfit for SBRT to investigate the optimal fractionation scheme.

Appropriate use criteria (AUC) are statements that contain indications describing when and how often an intervention should be performed under the optimal combination of scientific evidence, clinical judgment, and patient values while avoiding unnecessary provisions of services. Society of Nuclear

Purpose: We evaluated clinical outcomes of high-risk prostate cancer patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP).Materials and Methods: Patients were classified as high-risk prostate cancer and received definitive treatment between 2005 and 2015. Patients with previous pelvic radiotherapy, positive lymph node or distant metastasis were excluded. The primary outcomes were prostate cancer-specific survival (PCSS) and distant metastasis-free survival (DMFS). Results: Of 583 patients met the inclusion criteria (77 EBRT and 506 RP). The estimated 10-year PCSS was 97.0% in the RP and 95.9% in the EBRT (p = 0.770). No significant difference was seen in the DMFS (p = 0.540), whereas there was a trend in favor of RP over EBRT in overall survival (OS) (p = 0.068). Propensity score matching analysis with confounding variables was done, with 183 patients (66 EBRT and 117 RP) were included. No significant difference in DMFS, PCSS or OS was found. Conclusion: Our data demonstrated similar oncologic PCSS, OS, and DMFS outcomes between EBRT and RP patients.

Objective: The pathogenesis of endometriosis has not been clearly explained. Inflammatory factors of ectopic implantation and the growth of ectopic endometrial cells have been subjects of major interest. The number of studies evaluating salusin-α and nesfatin-1 markers in patients with endometriosis is limited. No studies have evaluated the levels of anti-inflammatory markers for adropin and netrin-1 in patients with endometriosis. This study investigates how some important inflammatory regulatory markers in the inflammatory process affect the pathogenesis of endometriosis and determines whether any relationship exists between serum levels of these parameters and endometriosis and insulin resistance. Materials and methods: This prospective study included 73 patients with endometriosis diagnosed histopathologically after laparoscopic surgery and 75 healthy controls. Serum adropin, salusin-α, netrin-1, and nesfatin-1 levels and homeostatic model assessment of insulin resistance (HOMA-IR) values of the participants were measured. Results: The endometriosis group had significantly lower nesfatin-1 levels than the control group (3.0±0.53 vs 9.5±0.94, p=0.005). Between the patient and control groups, there was no difference regarding serum adropin, salusin-α, and netrin-1 levels (p=0.36, p=0.34, p=0.75, respectively). Nesfatin-1 had a significant positive correlation with adropin, salusin-α, and netrin-1 (r=0.563, p

INTRODUCTION Nowadays micro-invasive-procedures (off-pump, beating-heart) for mitral valve repair (MVRe) are abruptly expanding with the potential to be adopted as a valuable alternative to surgery. In the present manuscript, the authors review the available technologies intended to treat mitral regurgitation (MR) through transapical approach, including annuloplasty and chordal-repair options. ANNULOPLASTY To date, Valcare Amend is the only transapical MV ring to have been implanted in patients. The device allows for stabilization of the annulus through a complete semirigid d-shaped ring. The first-in-human successful procedure was performed in 2016 by our Group and subsequent clinical experience included a total of 14 implanted patients. Currently, the technology is under clinical trial evaluation to validate the efficacy and safety profile of the device. CHORDAL REPAIR Beating-heart chordal implantation via transapical approach is a current feasible, safe and reproducible option. Neochord DS1000 is the most widely used technology in the field, with a solid procedural experience and good results in well-selected patients. Its clinical use has been validated in Europe since 2012, while it is still under clinical investigation in the United States. Harpoon MVRe system is a novel technology, recently CE-mark approved for clinical use. DISCUSSION AND CONCLUSIONS Transapical micro-invasive technologies are current viable therapies to treat MR in selected patients. Although there are still several limitations that preclude an extensive use of such procedures, their results are promising in well-selected patients. Embracing transcatheter MVRe therapies should guide the cardiac surgeon through the new revolution of micro-invasive MV tailored repair.

Purpose This prospective, observational first in human study evaluated the safety and effectiveness of WRAPSODYTM Cell-impermeable Endoprosthesis (Merit Medical Systems, Inc.) in the treatment of arteriovenous fistula and arteriovenous graft access circuit stenosis. Materials and Methods Investigators conducted a prospective analysis of 46 patients with access circuit stenosis from three centres. Treatment sites included the peripheral outflow veins (e.g. cephalic arch, basilic vein swing point; 16 fistula and 10 graft patients); the graft-vein anastomosis (9 patients); and the central veins (up to, but not including the SVC; 11 patients). Primary outcome measures included 30-day freedom from access circuit-related safety events and 30-day target lesion primary patency. Secondary outcome measures included procedural success; device- and procedure-related adverse events; target lesion primary patency; access circuit primary patency; and secondary patency. In-person follow-up was scheduled at 1, 3, 6, and 12 months. An independent data monitoring/clinical event committee adjudicated all reinterventions and device/procedure-relatedness for adverse events. Results All initial procedures were successful. All but one patient was free from safety events through the first 30 days (97.8% (45/46)). This event was not device-related. Over the remainder of the study, one adverse event was adjudicated as possibly device-related. Six- and 12-month target lesion primary patency rates were 97.7% (42/43) and 84.6.% (33/39), respectively. Six- and 12-month access circuit primary patency rates were 84.4% (38/45) and 65.9% (29/44), respectively. Conclusion Results suggest that the study device is safe and effective for treatment of stenoses in the peripheral and central veins of arteriovenous access circuits. Level of Evidence Level 2b, cohort study.

Background Limited COVID‐19 vaccination acceptance among healthcare assistants (HCAs) may adversely impact older adults, who are at increased risk for severe COVID‐19 infections. Our study objective was to evaluate the perceptions of COVID‐19 vaccine safety and efficacy in a sample of frontline HCAs, overall and by race and ethnicity. Methods An online survey was conducted from December 2020 to January 2021 through national e‐mail listserv and private Facebook page for the National Association of Health Care Assistants. Responses from 155 HCAs, including certified nursing assistants, home health aides, certified medical assistants, and certified medication technicians, were included. A 27‐item survey asked questions about experiences and perceptions of COVID‐19 vaccines, including how confident they were that COVID‐19 vaccines are safe, effective, and adequately tested in people of color. Multivariable regression was used to identify associations with confidence in COVID‐19 vaccines. Results We analyzed data from 155 completed responses. Among respondents, 23.9% were black and 8.4% Latino/a. Most respondents worked in the nursing home setting (53.5%), followed by hospitals (12.9%), assisted living (11.6%), and home care (10.3%). Respondents expressed low levels of confidence in COVID‐19 vaccines, with fewer than 40% expressing at least moderate confidence in safety (38.1%), effectiveness (31.0%), or adequate testing in people of color (27.1%). Non‐white respondents reported lower levels of confidence in adequate testing of vaccines compared to white respondents. In bivariate and adjusted models, respondents who gave more favorable scores of organizational leadership at their workplace expressed greater confidence in COVID‐19 vaccines. Conclusion Frontline HCAs reported low confidence in COVID‐19 vaccines. Stronger organizational leadership in the workplace appears to be an important factor in influencing HCA's willingness to be vaccinated. Action is needed to enhance COVID‐19 vaccine uptake in this important population with employers playing an important role to build vaccine confidence and trust among employees.

Autophagy plays a complicated role in the occurrence and development of cancer. Beclin 1 is a significant autophagy-related protein that plays an essential role in tumorigenesis, but its expression is controversial in melanoma. In this meta-analysis, we searched seven studies involving 638 melanoma patients. PubMed, Web of Science, Google Scholar, Elsevier, and Chinese National Knowledge Infrastructure were used for literature retrieval. The I2 index was used to assess heterogeneity. The expression of Beclin 1 in the primary melanoma group was significantly lower than the non-tumor group tissues (P0.01), while higher than the metastatic melanoma group (P0.01). Beclin 1 expression status could not distinguish between patients with melanoma by sex (male vs. female), lymph node metastasis (metastasis vs. non-metastasis), melanin deposition (present vs. absent), ulcer formation (present vs. absent), tumor necrosis status (present vs. absent), and Breslow thickness (1.5 mm vs. ≥1.5 mm) for the subgroups (all P values0.05). Different expression intensities of Beclin 1 did not affect the overall survival and disease-free survival of melanoma patients. This study showed a trend of low expression of Beclin 1 in melanoma; patients with low expression of Beclin 1 were prone to the possibility of distant metastasis. The inconsistent profile of Beclin 1 expression in the prognosis of melanoma patients warrants further clinical investigation.

Objective: The aim of the study is to create a new model to predict successful outcome in assisted reproductive techniques. Materials and Methods: A retrospective cohort study was conducted in tertiary fertility center between 2010 and 2017. Nulliparous women younger than 45 years-old undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) for the first time were included; frozen embryo transfers, canceled induction cycles, freeze-all cycles were excluded. Two prediction models were built using multivariate logistic regression with a subset of the dataset and then were internally validated using bootstrapping methods. Results: Four hundred eighty eight women were included with 136 (27.9%) live births. The basal model was built using variable age, antral follicle count (AFC), and basal luteinizing hormone (LH) levels. Age over 37 years [odds ratio (OR): 0.07, 95% confidence interval (CI): 0.00-0.36] and AFC below 5 (OR: 0.15, 95% CI: 0.02-0.53) was associated with poorer outcomes whereas an LH level above 6 mIU/mL (OR: 2.24, 95% CI: 1.27-3.94) was associated with better outcomes. Optimism adjusted area under the curve (AUC) of this model was 0.68 (95% CI: 0.62-0.74). Combined model in addition to basal model variables included the length of induction cycle, the endometrial thickness at the day of transfer, grade and count of the transferred embryo. Cycles lasting more than ten days (OR: 2.23, 95% CI: 1.17-4.42), an endometrial thickness greater than 9 mm (OR: 2.07, 95% CI: 1.00-4.53) were associated with better outcomes. Optimism adjusted AUC of this model was 0.76 (95% CI: 0.70-0.81). Calibration of both models was good according to Hosmer Lemeshow test (p=0.979 and p=0.848, respectively). Conclusion: This internally validated prediction model has good calibration and can be used predicting outcomes in first time IVF/ICSI cycles with modest sensitivity.

Objective: This study aims to investigate the distribution of antibodies that cause hemolytic disease of the fetus and newborn (HDFN) and compare the clinical outcomes of pregnancies affected by anti-D and anti-D combined with non-D Rh alloimmunization. Materials and Methods: We retrospectively searched and obtained the perinatal and neonatal data of patients with anti-D antibodies and anti-D combined with non-D Rh antibodies (anti-c, -C, -e, -E, and -Kell) from October 2015 to December 2018 at the University of Health Sciences Turkey, Kanuni Sultan Süleyman Training and Research Hospital. Univariate and multiple logistic regression analyses and adjusted odds ratios with their confidence intervals were used to define independent risk factors for non-D antibody positive. Results: The severe fetal hydrops rate was significantly higher in the anti-D combined non-D group (3/25, 12%) than in the anti-D group (1/128, 0.08%, p

Objective: We aim to study the relationship between atherosclerosis and serum sclerostin levels in different phenotypes of polycystic ovary syndrome (PCOS). Materials and Methods: A total of 134 women with PCOS and 33 age-matched controls participated in this study. Women with PCOS were further divided into subgroups based on their PCOS phenotypes: phenotype A (n=35), phenotype B (n=33), phenotype C (n=31), and phenotype D (n=35). Metabolic parameters, hormonal parameters, carotid intima-media thickness (CIMT), and sclerostin levels were compared among the PCOS phenotypes. Results: Statistically significant differences occurred among groups regarding follicle-stimulating hormone, luteinizing hormone, estradiol, total cholesterol, low-density lipoprotein, Ferriman-Gallwey score, total testosterone, and free androgen index. The mean CIMT was statistically higher in all PCOS phenotypes than in controls. In subgroup comparison, phenotypes A and B had a higher body mass index (BMI) adjusted CIMT than other phenotypes, respectively (p=0.005). Serum sclerostin levels were higher in PCOS patients than in controls. A concentration of ≥6.297 ng/mL showed a sensitivity of 56% and a specificity of 69.7% to predict PCOS. The BMI-adjusted sclerostin level was significantly higher in phenotype C (20.3±0.7 ng/mL) than in other phenotypes. Conclusion: Patients with phenotypes A and B seem to have an increased risk for atherosclerosis. Although sclerostin was higher in PCOS patients, we could not demonstrate the relation between sclerostin and atherosclerosis in different PCOS phenotypes.

Purpose: The study aims to report late toxicities in locally advanced head-and-neck squamous cell carcinoma (LAHNSCC) treated with intensity-modulated radiation therapy (IMRT).Materials and Methods: A retrospective study was conducted on 103 patients of LAHNSCC treated with IMRT. We analyzed the cumulative incidence of late xerostomia, dysphagia, and aspiration at an interval of 6-month, 1-year, 2-year, and 3-year from the start of IMRT.Results: At a median follow up of 4.2 years (interquartile range, 3.5 to 6 years), the cumulative incidence of grade ≥2 late xerostomia was 5.5%, dysphagia was 6.9%, and aspiration was 11.1%. Logistic regression showed that Dmean of ≥26 Gy to parotids had higher risk of xerostomia (hazard ratio [HR] = 5.19; 95% confidence interval [CI], 1.90–14.22; p = 0.001). Late dysphagia was associated with Dmean of ≥45 Gy to pharyngeal constrictors (PC) (HR = 7; 95% CI, 1.84–26.61; p =0.004), ≥55 Gy to larynx (HR = 3.25; 95% CI, 1.15–9.11; p = 0.025), and adjuvant RT (HR = 5.26; 95% CI, 1.85–14.87; p = 0.002). Aspiration was associated with Dmean of ≥45 Gy to larynx (HR = 6.5; 95% CI, 1.93–21.88; p = 0.003), Dmean of ≥55 Gy to PC (HR = 3.54; 95% CI, 1.25–9.98; p = 0.017), and patients having late dysphagia (HR = 4.37; 95% CI, 1.55–12.31; p = 0.005).Conclusions: IMRT is a feasible radiation delivery technique in LAHNSCC with a decreased late toxicity profile.

Background Accelerometry is an emerging option for real-time evaluation of functional capacity in patients with pulmonary arterial hypertension (PAH). This prospective pilot study assesses the relationship between functional capacity by accelerometry and right ventricular measurements on echocardiography for this high-risk cohort. Methods Patients with PAH were prospectively enrolled and underwent 6-Minute Walk Test and cardiopulmonary exercise testing. They were given a Fitbit, which collected steps and sedentary time per day. Echocardiographic data included right ventricular global longitudinal, free wall, and septal strain; tricuspid regurgitant peak velocity; tricuspid annular plane systolic excursion; tricuspid annular plane systolic velocity; right ventricular myocardial performance index; and pulmonary artery acceleration time. Pairwise correlations were performed. Results The final analysis included 22 patients aged 13 to 59 years. Tricuspid regurgitant peak velocity had a negative correlation with 6-Minute Walk Test (r = −0.58, P = .02), peak oxygen consumption on exercise testing (r = −0.56, P = .03), and average daily steps on accelerometry (r = −0.59, P = .03), but a positive correlation with median sedentary time on accelerometry (r = 0.64, P = .02). Pulmonary artery acceleration time positively correlated with peak oxygen consumption on exercise testing (r = 0.64, P = .002). There was no correlation between right ventricular strain measurements and functional capacity testing. Conclusion In this pilot study, tricuspid regurgitant jet and pulmonary artery acceleration time were the echocardiographic variables that correlated most with accelerometry data. With further echocardiographic validation, accelerometry can be a useful, noninvasive, and cost-effective tool to monitor disease progression in patients with PAH.

Background Periprocedural myocardial injury is a predictor of cardiovascular morbidity and mortality after percutaneous coronary intervention. Methods The authors examined the effects of preprocedural lipid levels (low-density lipoprotein, high-density lipoprotein, and triglycerides) in 977 patients with coronary artery disease who underwent elective percutaneous coronary intervention. Results Elevated cardiac troponin I level (≥5× the upper limit of normal) was used to indicate periprocedural myocardial injury. Serum lipid samples were collected 12 hours preprocedurally. Cardiac troponin I was collected 1, 6, and 12 hours postprocedurally. Correlations between preprocedural lipid levels and postprocedural cardiac troponin I were studied. Low-density lipoprotein levels were less than 70 mg/dL in 70% of patients and greater than 100 mg/dL in only 7.4% of patients; 13% had triglyceride levels greater than or equal to 150 mg/dL, and 96% had high-density lipoprotein levels less than 40 mg/dL. Patients with elevated cardiac troponin I had significantly lower left ventricular ejection fraction than did those with cardiac troponin I levels less than 5× the upper limit of normal (P = .01). Double-and triple-vessel disease were more common in patients with elevated cardiac troponin I (P < .002). Multivariable logistic and linear regression analyses revealed no statistically significant associations between lipid levels and postprocedural cardiac troponin I elevation, possibly because such large proportions of included patients had low levels of low-density lipoprotein (70%) and a history of statin intake (86%). Conclusion The authors found no association between lipid profile and periprocedural myocardial injury.

Background The failure rate of vascular closure devices remains a significant cause of major vascular complications in contemporary transcatheter aortic valve implantation practice. Methods This research aimed to evaluate use of the Angio-Seal device in a bailout context in the setting of incomplete hemostasis following use of dual Perclose ProGlide devices in patients undergoing transfemoral transcatheter aortic valve implantation. A total of 185 patients undergoing transfemoral transcatheter aortic valve implantation with either dual Per-close ProGlide (n = 139) or a combination of dual Perclose ProGlide and Angio-Seal (n = 46) were retrospectively analyzed. The baseline, procedural characteristics, and all outcomes (defined according to Valve Academic Research Consortium-2 criteria) were compared. Results No significant differences were seen between the dual Perclose ProGlide vs dual Perclose ProGlide+Angio-Seal groups with regard to the in-hospital Valve Academic Research Consortium-2 primary end points of major vascular complications (n = 13 [9.4%] vs n = 2 [4.3%]; P = .36), minor vascular complications (n = 13 [9.4%] vs n = 8 [14.7%]; P = .14), major bleeding (n = 16 [11.5%] vs n = 2 [4.3%]; P = .25), and minor bleeding (n = 9 [6.5%] vs n = 5 [10.9%]; P = .34), with higher rates of hematoma in the dual Perclose ProGlide+Angio-Seal group (n = 4 [2.9%] vs n = 5 [10.9%]; P = .044). Conclusion Finding from the current study suggest that adjunctive Angio-Seal deployment may be feasible and safe, especially in patients with incomplete hemostasis following dual Perclose ProGlide use, and can be an optimal “bailout” procedure.

Background Mitral valve stenosis (MS) is the primary pathologic feature of rheumatic mitral valve disease, and the complex repair affects its clinical outcome. This study aimed to examine the efficacy of the 4-step commisuroplasty “SCORe” procedure by assessing changes in the mobility of mitral valve leaflets and its clinical effects. Methods From September 1, 2018, to January 13, 2019, patients with MS who underwent mitral valve repair with the SCORe procedure in the study center were analyzed in this prospective study. Mitral valve structure was assessed by transthoracic echocardiography pre- and postoperatively as well as during follow-up. Results In total, 60 consecutive patients were examined. In 56 patients (93.3%), mitral valve orifice area (MVOA) was less than 1.5 cm2, and mean (SD) MVOA for the whole cohort was 1.20 (0.34) cm2. The mobility of the anterior leaflet was improved (P < .001) during the cardiac cycle postsurgery, but that of the posterior leaflet was not (P = .591). The mean (SD) coaptation length was increased significantly from 6.69 (1.32) mm to 7.92 (1.24) mm (P < .001) postoperatively. Mean (SD) MVOAs increased to 2.24 (0.38) cm2 postoperatively (P < .001). During the 1-year follow-up, there were no deaths or reoperations. Follow-up echocardiography revealed minor or mild regurgitation in 98.3% of patients. Conclusion These findings demonstrated that the SCORe procedure can effectively improve the mobility of mitral leaflets and enlarge the valve orifice area in patients with rheumatic MS in China, with minimal complications and promising results.

This study evaluated the safety, dosimetry, and characteristics of 3-((2-fluoro-4-(5-(2′-methyl-2-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)(methyl-(11)C)amino)propanoic acid ((11)C-CS1P1), a radiotracer targeting sphingosine-1-phosphate receptor (S1PR) 1 (S1PR1). S1PR1 is of clinical interest because of its role in multiple sclerosis (and other conditions), with an expanding class of S1PR modulators approved for relapsing multiple sclerosis. (11)C-CS1P1 binds S1PR1 with high specificity and has shown promise in animal models of inflammatory diseases. Methods: (11)C-CS1P1 was injected into 5 male and 6 female healthy participants. Ten participants were imaged with PET using a multipass whole-body continuous-bed-motion acquisition, and one had dedicated head and neck PET and MRI. Participants were continuously monitored for safety events. Organ time–activity curve data were collected, integrated, and normalized to the injected activity. Organ radiation doses and effective dose were computed using the adult male and female models in OLINDA, version 2.2. SUV images were evaluated for qualitative biodistribution. Results: No adverse events were observed after the dose, including no bradycardia. The liver was the critical organ from dosimetry analysis (mean ± SD: female, 23.12 ± 5.19 μSv/MBq; male, 21.06 ± 1.63 μSv/MBq). The whole-body effective dose (as defined by International Commission on Radiological Protection publication 103) was 4.18 ± 0.30 μSv/MBq in women and 3.54 ± 0.14 μSv/MBq in men. Using a maximum delivered dose of 740 MBq (20 mCi), the effective dose for women would be 3.1 mSv (0.31 rem), with a liver dose of 17.1 mSv (1.7 rem); the effective dose for men would be 2.6 mSv (0.26 rem), with a liver dose of 15.6 mSv (1.56 rem). Brain uptake was seen predominantly in gray matter and correlated with regional S1PR1 RNA expression (r = 0.84). Conclusion: These results support the safety of (11)C-CS1P1 for evaluation of inflammation in human clinical populations. Dosimetry permits repeated measures in the same participants. Brain uptake correlates well with known target topography.

Background Cardiogenic shock–related mortality is substantial, and temporary mechanical circulatory support (MCS) devices are frequently used. The authors aimed to describe patient characteristics and outcomes in patients with worsening cardiogenic shock requiring escalation of temporary MCS devices. Methods Worsening cardiogenic shock was defined as persistent hypotension, increasing doses of vasopressors/inotropes, worsening hypoperfusion, or worsening invasive hemo-dynamics. Escalation of temporary MCS devices was defined as adding or exchanging an existing MCS device. Variables were evaluated by logistic regression models and receiver operating characteristic curves. Results From July 1, 2016, to July 1, 2018, a total of 81 consecutive patients experienced worsening cardiogenic shock requiring temporary MCS escalation. The etiology of cardiogenic shock was heterogeneous (33.3% acute myocardial infarction and 61.7% decompen-sated heart failure). Younger age (85 mm Hg), and lower postescalation lactate levels ( Conclusion Patients requiring temporary MCS escalation represent a high-risk cohort. Further work is needed to improve outcomes in this patient population.

Background Right ventricle (RV) dysfunction after a coronary artery bypass grafting procedure is a challenge that adversely affects RV filling pressure and contraction. This study sought to determine whether additional bypass of an RV branch would lessen RV dysfunction. Methods Patients with severe right coronary artery (RCA) stenosis were divided into 2 groups. Group 1 patients (n = 50) had a single distal bypass on the RCA. Group 2 patients (n = 50) had both distal RCA and additional bypass on the RV branch of the RCA. Right ventricular function was examined by echocardiogram by measuring transannular plane systolic excursion, fractional area change, tissue Doppler S-wave velocity, and inferior vena cava diameter. Results Transannular plane systolic excursion and fractional area change measurements rapidly decreased below the cutoff in both groups, but group 2 patient values reached normal limits at 90 days. Tissue Doppler S-wave velocity reached the normal limit in 7 days. Inotropic agents were required in 11 patients in group 1 and 2 patients in group 2 (P = .013). The mean (SD) intensive care unit stay was 2.11 (1.12) days and 1.45 (0.71) days (P = .033), and the hospital stay was 7.32 (1.44) days and 6.22 (0.45) days in groups 1 and 2, respectively (P = .027). Conclusion The data in this study suggest that an additional graft on the RV branch of the RCA (eg, conus, marginal, any good runoff vessels on the RV) prevents severe RV dysfunction and allows for rapid recovery of RV dysfunction after off-pump coronary surgery.

Background Ablation of atrial tachyarrhythmia in adults with congenital heart disease (ACHD) is challenging because of complex anatomy and high scar burden. We proposed that the addition of high-density mapping with the PentaRay® (Biosense Webster, Inc) mapping catheter (EAM+P) to 3-dimensional electroanatomic mapping (EAM) allows for rapid acquisition of high-resolution maps and shorter procedure times. Methods In this single-center, retrospective cohort study of patients with ACHD who underwent atrial arrhythmia ablation, patients were divided those who underwent ablation with EAM and those who underwent ablation with EAM+P. Results Fifteen ablations were performed in 13 patients using standard EAM, and 11 ablations were performed in 10 patients using EAM+P. There was no difference in mean age or complexity of congenital heart disease. The procedure duration was 1.5 times longer in the EAM than in the EAM+P group (P = .015). The dose area product was 12 times higher in the EAM than in the EAM+P group (P = .001). A higher number of venous access sites were used for EAM cases than for EAM+P cases (P = .008). Acute success rates of ablation and recurrence rates at 1 year were similar in the 2 groups. There were no procedure-related complications in either group. Conclusion This is the first study to evaluate the use of the PentaRay® high-density mapping catheter for ablation of atrial tachyarrhythmia in patients with ACHD. The use of the PentaRay® high-density mapping catheter results in shorter procedure time, decreased radiation exposure, and fewer venous access sites.

Background Since the introduction of cardiac resynchronization therapy (CRT) to improve left ventricular function, the effect of CRT on the right ventricle in patients with heart failure has not been well described. Methods We evaluated the effect of CRT on right ventricular systolic function in 20 patients (80% men; mean [SD] age, 58.5 [9.8] y) with cardiomyopathy and right ventricular systolic dysfunction (New York Heart Association class III or IV, left ventricular ejection fraction ≤35%, and QRS interval ≥120 ms). The median follow-up time was 15 months. Right ventricular systolic function, defined as a tricuspid annular plane systolic excursion (TAPSE) index of 16 mm or less, was evaluated in patients before and after CRT. Results Twelve (60%) patients had ischemic cardiomyopathy, and 12 (60%) patients had left bundle branch block detected using surface electrocardiogram. The mean (SD) QRS duration was 160.5 (24.4) ms. From before CRT to the time of follow-up after CRT, the mean (SD) ejection fraction increased significantly from 22.5% (5.6%) to 29.4% (7.4%) (P < .001). The mean (SD) TAPSE index also increased significantly from 13.70 (1.78) mm to 16.50 (4.77) mm (P = .018). Eleven (55%) patients showed improved right ventricular systolic function (TAPSE ≥16 mm) after CRT. Patients with a favorable right ventricular response to CRT were significantly older (64.6 [8.2] y vs 53.6 [8.4] y, respectively) and more likely to have nonischemic origin of cardiomyopathy than were patients with unimproved right ventricular function (66.7% vs 18.2%, respectively). Conclusion Our findings indicate that CRT is associated with improved right ventricular systolic function in patients with heart failure and right ventricular systolic dysfunction. Patients with nonischemic heart disease more often show improved right ventricular function after CRT.

In this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed (89)Zr-DFO-durvalumab (anti–PD-L1 [programmed death ligand 1]) PET/CT in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) before monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of (89)Zr-DFO-durvalumab PET imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate (89)Zr-DFO-durvalumab uptake to tumor PD-L1 expression, (18)F-FDG uptake, and treatment response of individual lesions. Methods: In this prospective multicenter phase I–II study (NCT03829007), patients with incurable R/M SCCHN underwent baseline (18)F-FDG PET and CT or MRI. Subsequently, PD-L1 PET imaging was performed 5 d after administration of 37 MBq of (89)Zr-DFO-durvalumab. To optimize imaging conditions, dose finding was performed in the first 14 patients. For all patients (n = 33), durvalumab treatment (1,500 mg/4 wk, intravenously) was started within 1 wk after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum, 24 mo). CT evaluation was assessed according to RECIST 1.1 every 8 wk. PD-L1 expression was determined by combined positive score on (archival) tumor tissue. (89)Zr-DFO-durvalumab uptake was measured in (18)F-FDG–positive lesions, primary and secondary lymphoid organs, and blood pool. Results: In total, 33 patients with locoregional recurrent (n = 12) or metastatic SCCHN (n = 21) were enrolled. (89)Zr-DFO-durvalumab injection was safe. A dose of 10 mg of durvalumab resulted in highest tumor-to-blood ratios. After a median follow-up of 12.6 mo, overall response rate was 26%. The disease control rate at 16 wk was 48%, with a mean duration of 7.8 mo (range, 1.7–21.1). On a patient level, (89)Zr-DFO-durvalumab SUV(peak) or tumor-to-blood ratio could not predict treatment response (hazard ratio, 1.5 [95% CI, 0.5–3.9; P = 0.45] and 1.3 [95% CI, 0.5–3.3; P = 0.60], respectively). Also, on a lesion level, (89)Zr-DFO-durvalumab SUV(peak) showed no substantial correlation to treatment response (Spearman ρ, 0.45; P = 0.051). Lesional (89)Zr-DFO-durvalumab uptake did not correlate to PD-L1 combined positive score but did correlate to (18)F-FDG SUV(peak) (Spearman ρ, 0.391; P = 0.005). Conclusion: PINCH is the first, to our knowledge, PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of (89)Zr-DFO-durvalumab PET/CT in a multicenter trial. (89)Zr-DFO-durvalumab uptake did not correlate to durvalumab treatment response.

(18)F-FDG PET has limited diagnostic applications in malignant melanoma (MM). (18)F-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ((18)F-PFPN) is a novel PET probe with high affinity and selectivity for melanin. We conducted a clinical study with 2 aims, first to investigate the biodistribution and radiation dosimetry of (18)F-PFPN in healthy volunteers, and second, to examine the diagnostic utility of (18)F-PFPN PET imaging in patients with MM. Methods: (18)F-PFPN was synthesized through a fluoro-for-tosyl exchange reaction. Five healthy volunteers were enrolled to investigate the biodistribution, pharmacokinetics, radiation dosimetry, and safety of the tracer. Subsequently, a total of 21 patients with clinically suspected or confirmed MM underwent both (18)F-PFPN PET/MRI and (18)F-FDG PET/CT scans. The normalized SUV(max) of selected lesions was determined for both tracers and compared in patient- and lesion-based analyses. Results: (18)F-PFPN has an elevated radiochemical yield and was highly stable in vivo. In healthy volunteers, (18)F-PFPN was safe and well tolerated, and its effective absorbed dose was comparable to that of (18)F-FDG. In patient-based analysis, (18)F-PFPN uptake was higher than (18)F-FDG for both primary tumors and nodal metastases. In lesion-based analysis,(18)F-PFPN PET imaging could detect 365 metastases that were missed on (18)F-FDG PET. Additionally, (18)F-PFPN PET imaging had clinical value in distinguishing false-positive lesions on (18)F-FDG PET. Conclusion: (18)F-PFPN is a safe and well-tolerated melanin PET tracer. In a pilot clinical study, (18)F-PFPN PET imaging outperformed traditional (18)F-FDG PET in identifying both primary MM and its distant spread.

The fetal absorbed dose from (18)F-FDG administration to the mother is an essential piece of information when considering the use of PET to stage cancers during pregnancy. However, the few existing human case reports were obtained using either PET-only or PET/CT machines, which may not accurately identify the soft tissues of the fetus for dosimetric calculations. This study presents data from 11 women injected with (18)F-FDG for cancer staging during the first 2 trimesters of pregnancy and is, to our knowledge, the first to be entirely acquired with PET/MRI. Methods: Eleven pregnant women (12 scans) with cervical cancer were imaged with (18)F-FDG PET/MRI, and their images were retrospectively analyzed for this study. The fraction of injected activity concentrated by the fetus was derived from manually drawing regions of interest on the MRI slices. From the activity fraction, the fetal time-integrated coefficients were derived and combined with the standard coefficients of the mothers’ organs from the ICRP publication 106. The fetal absorbed doses were calculated with OLINDA/EXM 1.1 and a dynamic bladder model. Results: All fetuses after early pregnancy could be accurately delineated because of the coregistered MRI scans. (18)F-FDG activity was unevenly distributed in the fetal body: the hearts and urinary bladders were generally visible, whereas the brain showed lower uptake. The estimated fetal doses were 2.21E−02 mGy/MBq for 1 woman imaged in early pregnancy, 7.38 ± 0.25 E−03 mGy/MBq for 3 women imaged at the end of the first trimester, and 4.92 ± 1.53 E−03 mGy/MBq for 8 women imaged during the second trimester. Conclusion: PET/MR images of pregnant women injected with (18)F-FDG confirm that the fetal (18)F-FDG dose is very low. Therefore, clinically appropriate (18)F-FDG scans in women with cancer should not be withheld because of pregnancy.

Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on heart rate recovery in these patients. We retrospectively reviewed charts of patients with AFD who underwent maximal effort cardiopulmonary exercise testing (CPET) (n=44; 38.2 ± 13.8 yr; 23 men) from 2012 through 2018. Electrocardiographic, Holter monitoring, echocardiographic, cardiac magnetic resonance imaging, and patient demographic data were collected. No patient had adverse events that necessitated CPET termination, whereas 25 (57%) had ectopy during CPET, including 3 (7%) with frequent premature atrial contractions and 5 (11%) with frequent premature ventricular contractions. The ectopic burden was higher during resting electrocardiographic monitoring before exercise. In addition, 7 patients (16%) had pathologic ST-segment or T-wave changes on CPET, defined as ST-segment changes ≥2 mm. Among the patients who had concurrent cardiac magnetic resonance findings with their CPET (n=27), ST-segment or T-wave changes were associated with left ventricular myocardial mass (r=0.43, P=0.02). Chronotropic incompetence was seen during CPET in 28 patients (64%); however, only 2 patients (4%) had abnormal heart rate recovery at 1 minute. This study shows that patients with AFD can safely undergo exercise testing but have a high incidence of exercise-induced arrhythmias and ischemic changes. Ischemic electrocardiographic changes during exercise testing are associated with myocardial mass. Despite the chronotropic incompetence associated with AFD, heart rate recovery appears to be generally preserved in these patients.

The clinical course for patients with neuroendocrine neoplasms (NENs) ranges from indolent to highly aggressive. Noninvasive tools to improve prognostication and guide decisions on treatment are warranted. Expression of urokinase plasminogen activator receptor (uPAR) is present in many cancer types and associated with a poor outcome. Therefore, using an in-house–developed uPAR PET tracer [(68)Ga]Ga-NOTA-Asp-Cha-Phe-D-Ser-D-Arg-Tyr-Leu-Trp-Ser-OH ((68)Ga-NOTA-AE105), we aimed to assess uPAR expression in NENs. We hypothesized that uPAR expression was detectable in a significant proportion of patients and associated with a poorer outcome. In addition, as uPAR-targeted radionuclide therapy has previously proven effective in preclinical models, the study would also indicate the potential for uPAR-targeted radionuclide therapy in NEN patients. Methods: In a prospective clinical phase II trial, we included 116 patients with NENs of all grades, of whom 96 subsequently had uPAR PET/CT performed with evaluable lesions. PET/CT was performed 20 min after injection of approximately 200 MBq of (68)Ga-NOTA-AE105. uPAR target-to-liver ratio was used to define lesions as uPAR-positive when lesion SUV(max)–to–liver SUV(mean) ratio was at least 2. Patients were followed for at least 1 y to assess progression-free and overall survival. Results: Most patients had small intestinal NENs (n = 61) and metastatic disease (n = 86). uPAR-positive lesions were seen in 68% (n = 65) of all patients and in 75% (n = 18) of patients with high-grade (grade 3) NENs. During follow-up (median, 28 mo), 59 patients (62%) experienced progressive disease and 28 patients (30%) died. High uPAR expression, defined as a uPAR target-to-liver ratio above median, had a hazard ratio of 1.87 (95% CI, 1.11–3.17) and 2.64 (95% CI, 1.19–5.88) for progression-free and overall survival, respectively (P < 0.05 for both). Conclusion: When (68)Ga-NOTA-AE105 PET was used to image uPAR in patients with NENs, uPAR-positive lesions were seen in most patients, notably in patients with both low-grade and high-grade NENs. Furthermore, uPAR expression was associated with a worse prognosis. We suggest that uPAR PET is relevant for risk stratification and that uPAR may be a promising target for therapy in patients with NENs.

Background In this retrospective study, we compared the results from 2 pulmonary valve augmentation techniques in patients undergoing surgical repair of tetralogy of Fallot. Methods Between 2015 and 2018, 18 patients had anterior pulmonary valve repair at our institution, and 26 patients had both anterior and posterior pulmonary valve repair. Results Patients ranged from 6 months to 30 years of age. The median follow-up period was 8 months in the anterior augmentation group and 5 months in the anterior and posterior augmentation group. Postoperative echocardiograms indicated that only 2 patients (11%) in the anterior augmentation group had moderate or severe pulmonary insufficiency, compared with no patients in the anterior and posterior augmentation group. At follow-up, pulmonary insufficiency was seen in 3 patients (17%) in the anterior augmentation group and no patients in the anterior and posterior augmentation group. Conclusion Reconstruction of the native pulmonary valve accompanied by pulmonary cusp augmentation can decrease or even circumvent postoperative pulmonary insufficiency. Both anterior augmentation and anterior and posterior augmentation techniques are easily applied; however, we believe that the anterior and posterior augmentation technique is superior in terms of early postoperative and follow-up pulmonary insufficiency outcomes.

Background Vascular complications (VCs) after transfemoral transcatheter aortic valve implantation (TAVI) have an increased mortality risk, and vascular closure device (VCD) use is mandatory. The percutaneous MANTA VCD (Teleflex) is a novel collagen-based technology for closure of large-bore arteriotomies. We compared the MANTA VCD with the suture-based ProGlide VCD (Abbott Vascular). Methods A retrospective review was performed on all consecutive patients who underwent transfemoral TAVI in our center from January 1, 2015, to February 28, 2021, and 30-day outcomes were recorded. Major adverse cardiovascular events (MACE) were cardiac death, disabling stroke, and/or major VCs. Access site–related VCs were VCs related to the access site vessel from which the transcatheter valve was introduced and advanced. Results The MANTA VCD was used in 99 patients and the ProGlide in 224. There was 4.0% MACE in the MANTA group and 4.9% in the ProGlide group (P = .999). Overall VCs were 10.1% vs 7.6%, major VCs were 3.0% vs 2.2%, and minor VCs 7.1% vs 5.4%(P = .753). Access site–related VCs were 5.1% vs 5.8% in the (P = .999), and periprocedural vascular surgical intervention was needed in 6.1% of the MANTA group vs 2.2% of the ProGlide group (P = .099). Conclusion There was no significant difference in MACE, mortality, cardiovascular mortality, VCs, access site–related VCs, periprocedural vascular surgical interventions, bleeding, or transfusion rate between the 2 groups. The MANTA VCD group had more periprocedural vascular surgical interventions which did not reach statistical significance.

Background There are limited data on the outcomes of acute myocardial infarction–cardiogenic shock (AMI-CS) in patients with concomitant cancer. Methods A retrospective cohort of adult AMI-CS admissions was identified from the National Inpatient Sample (2000–2017) and stratified by active cancer, historical cancer, and no cancer. Outcomes of interest included in-hospital mortality, use of coronary angiography, use of percutaneous coronary intervention, do-not-resuscitate status, palliative care use, hospitalization costs, and hospital length of stay. Results Of the 557,974 AMI-CS admissions during this 18-year period, active and historical cancers were noted in 14,826 (2.6%) and 27,073 (4.8%), respectively. From 2000 to 2017, there was a decline in active cancers (adjusted odds ratio, 0.70 [95% CI, 0.63–0.79]; P < .001) and an increase in historical cancer (adjusted odds ratio, 2.06 [95% CI, 1.89–2.25]; P < .001). Compared with patients with no cancer, patients with active and historical cancer received less-frequent coronary angiography (57%, 67%, and 70%, respectively) and percutaneous coronary intervention (40%, 47%, and 49%%, respectively) and had higher do-not-resuscitate status (13%, 15%, 7%%, respectively) and palliative care use (12%, 10%, 6%%, respectively) (P < .001). Compared with those without cancer, higher in-hospital mortality was found in admissions with active cancer (45.9% vs 37.0%; adjusted odds ratio, 1.29 [95% CI, 1.24–1.34]; P < .001) but not historical cancer (40.1% vs 37.0%; adjusted odds ratio, 1.01 [95% CI, 0.98–1.04]; P = .39). AMI-CS admissions with cancer had a shorter hospitalization duration and lower costs (all P < .001). Conclusion Concomitant cancer was associated with less use of guideline-directed procedures. Active, but not historical, cancer was associated with higher mortality in patients with AMI-CS.

Prostate-specific membrane antigen (PSMA) tracers have increased sensitivity in the detection of prostate cancer, compared with conventional imaging. We assessed the management impact of (18)F-DCFPyL PSMA PET/CT in patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and report early biochemical response in patients who underwent radiation treatment. Methods: One hundred patients were enrolled into a prospective study, with a prior RP for prostate cancer, a PSA of 0.2–2.0 ng/mL, and no prior treatment. All patients underwent diagnostic CT and PSMA PET/CT, and management intent was completed at 3 time points (original, post-CT, and post-PSMA) and compared. Patients who underwent radiotherapy with 6-mo PSA response data are presented. Results: Ninety-eight patients are reported, with a median PSA of 0.32 ng/mL (95% CI, 0.28–0.36), pT3a/b disease in 71.4%, and an International Society of Urological Pathology grade group of at least 3 in 59.2%. PSMA PET/CT detected disease in 46.9% of patients, compared with 15.5% using diagnostic CT (PSMA PET, 29.2% local recurrence and 29.6% pelvic nodal disease). A major change in management intent was higher after PSMA than after CT (12.5% vs. 3.2%, P = 0.010), as was a moderate change in intent (31.3% vs. 13.7%, P = 0.001). The most common change was an increase in the recommendation for elective pelvic radiation (from 15.6% to 33.3%), nodal boost (from 0% to 22.9%), and use of concurrent androgen deprivation therapy (ADT) (from 22.9% to 41.7%) from original to post-PSMA intent because of detection of nodal disease. Eighty-six patients underwent (18)F-DCFPyL–guided radiotherapy. Fifty-five of 86 patients either did not receive ADT or recovered after ADT, with an 18-mo PSA response from 0.32 to 0.02 ng/mL; 94.5% of patients had a PSA of no more than 0.20 ng/mL, and 74.5% had a PSA of no more than 0.03 ng/mL. Conclusion: (18)F-DCFPyL PET/CT has a significant impact on management intent in patients being considered for salvage radiotherapy after RP with PSA recurrence. Increased detection of disease, particularly in the pelvic lymph nodes, resulted in increased pelvic irradiation and concurrent ADT use. Early results in patients who are staged with (18)F-DCFPyL PET/CT show a favorable PSA response.

Background Neoaortic sinus dilatation is a late comorbidity after an arterial switch operation in patients with dextro-transposition of the great arteries. We aim to explore whether neoaortic sinus dilatation is related to overweight or obesity, as these affect aortic remodeling in such patients. Methods We measured neoaortic diameters including those for the annulus, sinus, sinotubular junction, and ascending aorta by echocardiography and studied the relationship between these diameters and body mass index in patients aged 15 years and older after an arterial switch operation. Results A total of 45 patients were studied. Median (interquartile range) age, body mass index, and systolic blood pressure at echocardiography were 20 (17–28) years, 21.2 (18.4–24.2) kg/m2, and 120 (112–127) mm Hg, respectively. Echocardiogram revealed the following median values (interquartile ranges): neoaortic annulus diameter, 22.2 (19.8–23.8) mm; sinus diameter, 34.6 (31.8–39.8) mm; sinotubular junction diameter, 27.5 (22.4–30.0) mm; and ascending aortic diameter, 20.4 (19.4–22.7) mm. The neoaortic sinus diameter was significantly correlated with body mass index (r = 0.41, P = .004) and was significantly larger in patients with concomitant ventricular septal defect (P < .001) and those who were over-weight (body mass index ≥25 kg/m2; P = .006). Conclusion Neoaortic sinus dilatation after an arterial switch operation is associated with being overweight during adolescence and young adulthood. It is important to prevent obesity in patients after an arterial switch operation and educate them on a healthy lifestyle.

Background Patients with atrial fibrillation are at risk for ischemic stroke, even with low CHA2DS2-VASc scores. The left atrial appendage is a known site of thrombus formation in individuals with atrial fibrillation. Methods We conducted a prospective study, enrolling patients with nonvalvular atrial fibrillation and CHA2DS2-VASc scores of 0 or 1. Patients were divided into groups based on left atrial appendage morphology (determined by computed tomography): the “chicken wing” group and the non–chicken wing group. We followed patients for more than 1 year to observe the incidence of stroke. Results Of 509 patients with a mean (SD) age of 48.9 (11.6) years; 332 (65.2%) were men. The chicken wing group had fewer left atrial appendage lobes, a lower left atrial appendage depth, and a smaller left atrial appendage orifice area (all P < .001). During the follow-up period, 5 of the 133 patients (3.8%) in the chicken wing group and 56 of the 376 patients (14.9%) in the non–chicken wing group experienced ischemic stroke (P < .001). The following findings were significantly associated with the incidence of stroke: left atrial appendage depth (hazard ratio [HR], 1.98; 95% CI, 1.67-3.12; P = .03), left atrial appendage orifice area (HR, 2.16; 95% CI, 1.59–3.13; P < .001), and non–chicken wing left atrial appendage morphology (HR, 1.16; 95% CI, 1.10–1.23; P < .001). Conclusion For patients with atrial fibrillation and a low CHA2DS2-VASc score, the non–chicken wing left atrial appendage morphology type is independently associated with ischemic stroke.

Background This study investigated the relationship between coronary collateral circulation (CCC) and intracoronary thrombus burden in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). CCC and thrombus burden are predictive of clinical outcomes in patients with STEMI. Methods Patients with STEMI undergoing primary percutaneous coronary intervention were enrolled (n = 172). CCC was graded according to the Cohen–Rentrop classification. Patients were classified as insufficient (grade 0 or 1, n = 134) or well-developed (grade 2 or 3; n = 38) CCC. The Thrombolysis in Myocardial Infarction scale was used to evaluate intra-coronary thrombus burden. The low-thrombus-burden group comprised those with grades 0 to 2, and the high-thrombus-burden group comprised those with grades 3 or 4. Results Right coronary artery infarcts had a 13.830-fold higher chance of having well-developed CCC than did left anterior descending artery infarcts (P < .001). Circumflex artery infarcts had a 7.904-fold higher chance of well-developed CCC than did left anterior descending artery infarcts (P = .016). High thrombus burden was associated with a 4.393-fold higher chance for well-developed CCC than was low thrombus burden (P = .030). Low albumin levels were related to a greater chance of having well-developed CCC (P = .046). Conclusion Patients with well-developed CCC have higher thrombus burden than do those with insufficient CCC. Because well-developed CCC is an indicator of more severe underlying lesions, we speculate that patients with severe lesions are more prone to experience more complicated STEMI with high thrombus burden.