Citations

Objectives This study aimed to explore clinicians’ perceptions of the occurrence of and factors associated with diagnostic errors in patients evaluated during a rapid response team (RRT) activation or unplanned admission to the intensive care unit (ICU). Methods A multicenter prospective survey study was conducted among multiprofessional clinicians involved in the care of patients with RRT activations and/or unplanned ICU admissions (UIAs) at 2 academic hospitals and 1 community-based hospital between April 2019 and March 2020. A study investigator screened eligible patients every day. Within 24 hours of the event, a research coordinator administered the survey to clinicians, who were asked the following: whether diagnostic errors contributed to the reason for RRT/UIA, whether any new diagnosis was made after RRT/UIA, if there were any failures to communicate the diagnosis, and if involvement of specialists earlier would have benefited that patient. Patient clinical data were extracted from the electronic health record. Results A total of 1815 patients experienced RRT activations, and 1024 patients experienced UIA. Clinicians reported that 18.2% (95/522) of patients experienced diagnostic errors, 8.0% (42/522) experienced a failure of communication, and 16.7% (87/522) may have benefitted from earlier involvement of specialists. Compared with academic settings, clinicians in the community hospital were less likely to report diagnostic errors (7.0% versus 22.8%, P = 0.002). Conclusions Clinicians report a high rate of diagnostic errors in patients they evaluate during RRT or UIAs.

Purpose: There is an increased risk for development of blepharoptosis after incisional glaucoma surgery. Data on safety and efficacy of ptosis repair in this group of patients in limited. The goal of this study is to evaluate outcomes and identify potential risk factors for failure of ptosis repair in eyes with history of incisional glaucoma surgery. Methods: A retrospective chart review was performed of all patients who underwent incisional glaucoma surgery, specifically trabeculectomy or implantation of glaucoma drainage device (GDD), and subsequent ptosis repair at a single institution from 2009 to 2019. Ptosis surgery outcomes were compared to a control group who underwent ptosis repair after cataract surgery. Results: Seventy-eight eyes of 64 patients were included in the glaucoma surgery group. The rate of severe ptosis (margin reflex distance 1 ⩽ 0 mm) among glaucoma surgery patients was higher compared to control (35 of 78 (44.9%) vs 23 of 82 (28.6%). Ptosis repair was successful in 59 of 78 eyes (75.6%), which was similar to control. Risk for revision surgery was increased more than five-fold in the GDD group compared to control. There were no cases of early or late bleb-related complications. Conclusions: Ptosis repair can be performed safely in patients after incisional glaucoma surgery. Müller muscle conjunctival resection and external levator advancement are equally effective. Patients with history of GDD should be advised about the potentially increased risk of need for revision surgery.

Purpose Understanding all factors that may impact radiation dose and procedural time is crucial to safe and efficient image-guided interventions, such as fluoroscopically guided sacroiliac (SI) joint injections. The purpose of this study was to evaluate the effect of flow pattern (intra- vs. periarticular), patient age, and body mass index (BMI) on radiation dose and fluoroscopy time. Methods A total of 134 SI joint injections were reviewed. Injectate flow pattern, age, and BMI were analyzed in respect to fluoroscopy time (minutes), radiation dose (kerma area product (KAP); µGy m 2 ), and estimated skin dose (mGy). Results BMI did not affect fluoroscopy time, but increased BMI resulted in significantly higher skin and fluoroscopy doses ( p < 0.001). There was no association between fluoroscopy time and flow pattern. Higher skin dose was associated with intraarticular flow ( p = 0.0086), and higher KAP was associated with periarticular flow ( p = 0.0128). However, the odds ratios were close to 1. There was no significant difference between fluoroscopy time or dose based on patient age. Conclusion Increased BMI had the largest impact on procedural radiation dose and skin dose. Flow pattern also showed a statistically significant association with radiation dose and skin dose, but the clinical difference was small. Proceduralists should be aware that BMI has the greatest impact on fluoroscopy dose and skin dose during SI joint injections compared to other factors.

PurposeChemical shift‐encoded MRI (CSE‐MRI) is well‐established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature‐controlled experiments, and a multi‐center, multi‐vendor phantom study.Theory and MethodsA technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude‐, complex‐, and hybrid‐based CSE‐MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine‐site multi‐vendor phantom study and compared to temperature‐corrected PDFF estimation using an a priori guess for ambient room temperature.ResultsSimulations and temperature‐controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude‐based CSE‐MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction.ConclusionCorrection for temperature reduces temperature‐related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude‐based CSE‐MRI, even without a priori information about the temperature.

OBJECTIVE The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non–small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31–86 years). The median follow-up was 7.6 months (range 0.5–81.6 months), and the median survival was 9.3 months (range 1.3–81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Biological sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Epidemiological data and observational reports from both the original SARS epidemic and the most recent COVID-19 pandemic have a common feature: males are more likely to exhibit enhanced disease severity and mortality than females. Sex differences in cardiovascular disease and COVID-19 share mechanistic foundations, namely, the involvement of both the innate immune system and the canonical renin-angiotensin system (RAS). Immunological differences suggest that females mount a rapid and aggressive innate immune response, and the attenuated antiviral response in males may confer enhanced susceptibility to severe disease. Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19, either to serve as a protective mechanism by deactivating the RAS or as the receptor for viral entry, respectively. Loss of membrane ACE2 and a corresponding increase in plasma ACE2 are associated with worsened cardiovascular disease outcomes, a mechanism attributed to a disintegrin and metalloproteinase (ADAM17). SARS-CoV-2 infection also leads to ADAM17 activation, a positive feedback cycle that exacerbates ACE2 loss. Therefore, the relationship between cardiovascular disease and COVID-19 is critically dependent on the loss of membrane ACE2 by ADAM17-mediated proteolytic cleavage. This article explores potential mechanisms involved in COVID-19 that may contribute to sex-specific susceptibility focusing on the innate immune system and the RAS, namely, genetics and sex hormones. Finally, we highlight here the added challenges of gender in the COVID-19 pandemic.

Abstract A key component of cardiac ischemia–reperfusion injury (IRI) is the increased generation of reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study, we hypothesized that oxidative stress, due to ischemia–reperfusion, induces senescence which contributes to the pathophysiology of cardiac IRI. We demonstrate that IRI induces cellular senescence in both cardiomyocytes and interstitial cell populations and treatment with the senolytic drug navitoclax after ischemia–reperfusion improves left ventricular function, increases myocardial vascularization, and decreases scar size. SWATH‐MS‐based proteomics revealed that biological processes associated with fibrosis and inflammation that were increased following ischemia–reperfusion were attenuated upon senescent cell clearance. Furthermore, navitoclax treatment reduced the expression of pro‐inflammatory, profibrotic, and anti‐angiogenic cytokines, including interferon gamma‐induced protein‐10, TGF‐β3, interleukin‐11, interleukin‐16, and fractalkine. Our study provides proof‐of‐concept evidence that cellular senescence contributes to impaired heart function and adverse remodeling following cardiac ischemia–reperfusion. We also establish that post‐IRI the SASP plays a considerable role in the inflammatory response. Subsequently, senolytic treatment, at a clinically feasible time‐point, attenuates multiple components of this response and improves clinically important parameters. Thus, cellular senescence represents a potential novel therapeutic avenue to improve patient outcomes following cardiac ischemia–reperfusion.

Abstract Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2+ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N = 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade. Hazard ratios and 2-sided P values for recurrence-free survival of the predicted large- (n = 387), moderate- (n = 401), and no-benefit (n = 104) groups, based on the 8-gene signature were 0.47 (95% CI = 0.31 to 0.73, P &lt; .001), 0.60 (95% CI = 0.39 to 0.92, P = .02), and 1.54 (95% CI = 0.59 to 4.02, P = .38), respectively (Pinteraction = .02), providing validation of the 8-gene signature in an independent study.