Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days (n = 649 [32.1%]), 4-7 days (n = 776 [38.3%]), 8-10 days (n = 263 [13.0%]), and greater than 10 days (n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days (n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support (n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

Mapping the correlations between bandgap, HOMO, and LUMO trends for meta substituted Zn-MOFs.

Bandgap is a key property that determines electrical and optical properties in materials. Modulating the bandgap thus is critical in developing novel materials particularly semiconductors with improved features. This study examines the bandgap, highest occupied molecular orbital (HOMO), and lowest unoccupied molecular orbital (LUMO) energy level trends in a metal organic framework, metal-organic framework 5 (MOF-5), as a function of Hammett substituent effect (with the constant σm in the meta-position of the benzene ring) and solvent dielectric effect (with the constant ε). Specifically, experimental design and response surface methodologies helped to assess the significance of trends and correlations between these molecular properties with σm and ε. While the HOMO and LUMO decrease with increasing σm, the LUMO exhibits greater sensitivity to the substituent's electron withdrawing capability. The relative difference in these trends helps to explain why the bandgap tends to decrease with increasing σm.

Factors associated with acute esophagitis during radiation therapy for lung cancer.

INTRODUCTION: Limiting acute esophagitis remains a clinical challenge during the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Demographic, dosimetric, and acute toxicity data were prospectively collected for patients undergoing definitive radiation therapy +/- chemotherapy for stage II-III NSCLC from 2012 to 2022 across a statewide consortium. Logistic regression models were used to characterize the risk of grade 2 + and 3 + esophagitis as a function of dosimetric and clinical covariates. Multivariate regression models were fitted to predict the 50 % risk of grade 2 esophagitis and 3 % risk of grade 3 esophagitis. RESULTS: Of 1760 patients, 84.2 % had stage III disease and 85.3 % received concurrent chemotherapy. 79.2 % of patients had an ECOG performance status ≤ 1. Overall rates of acute grade 2 + and 3 + esophagitis were 48.4 % and 2.2 %, respectively. On multivariate analyses, performance status, mean esophageal dose (MED) and minimum dose to the 2 cc of esophagus receiving the highest dose (D2cc) were significantly associated with grade 2 + and 3 + esophagitis. Concurrent chemotherapy was associated with grade 2 + but not grade 3 + esophagitis. For all patients, MED of 29 Gy and D2cc of 61 Gy corresponded to a 3 % risk of acute grade 3 + esophagitis. For patients receiving chemotherapy, MED of 22 Gy and D2cc of 50 Gy corresponded to a 50 % risk of acute grade 2 + esophagitis. CONCLUSIONS: Performance status, concurrent chemotherapy, MED and D2cc are associated with acute esophagitis during definitive treatment of NSCLC. Models that quantitatively account for these factors can be useful in individualizing radiation plans.

Factors Associated With Cardiac Radiation Dose Reduction After Hypofractionated Radiation Therapy for Localized, Left-Sided Breast Cancer in a Large Statewide Quality Consortium.

PURPOSE: Limiting cardiac radiation dose is important for minimizing long-term cardiac toxicity in patients with left-sided early-stage breast cancer. METHODS AND MATERIALS: Prospectively collected dosimetric data were analyzed for patients undergoing moderately hypofractionated radiation therapy to the left breast within the Michigan Radiation Oncology Quality Consortium from 2016 to 2022. The mean heart dose (MHD) goal was progressively tightened from ≤2 Gy in 2016 to MHD ≤ 1.2 Gy in 2018. In 2021, a planning target volume (PTV) coverage goal was added, and the goal MHD was reduced to ≤1 Gy. Multivariate logistic regression models were developed to assess for covariates associated with meeting the MHD goals in 2016 to 2020 and the combined MHD/PTV coverage goal in 2021 to 2022. RESULTS: In total, 4165 patients were analyzed with a median age of 64 years. Overall average cardiac metric compliance was 91.7%. Utilization of motion management increased from 41.8% in 2016 to 2020 to 46.5% in 2021 to 2022. Similarly, use of prone positioning increased from 12.2% to 22.2% in these periods. On multivariate analysis in the 2016 to 2020 cohort, treatment with motion management (odds ratio [OR], 5.20; 95% CI, 3.59-7.54; P < .0001) or prone positioning (OR, 3.21; 95% CI, 1.85-5.57; P < .0001) was associated with meeting the MHD goal, while receipt of boost (OR, 0.25; 95% CI, 0.17-0.39; P < .0001) and omission of hormone therapy (OR, 0.65; 95% CI, 0.49-0.88; P = .0047) were associated with not meeting the MHD goal. From 2021 to 2022, treatment with motion management (OR, 1.89; 95% CI, 1.12-3.21; P = .018) or prone positioning (OR, 3.71; 95% CI, 1.73-7.95; P = .0008) was associated with meeting the combined MHD/PTV goal, while larger breast volume (≥1440 cc; OR, 0.34; 95% CI, 0.13-0.91; P = .031) was associated with not meeting the combined goal. CONCLUSIONS: In our statewide consortium, high rates of compliance with aggressive targets for limiting cardiac dose were achievable without sacrificing target coverage.

National Long-term Survival Estimates After Radical Prostatectomy for Prostate Cancer.

OBJECTIVE: To examine survival and disease control outcomes, including metastasis-related survival outcomes, in a large contemporary cohort of patients undergoing radical prostatectomy for localized prostate cancer. METHODS: We conducted a retrospective study of men with localized prostate cancer treated with radical prostatectomy from 2005 to 2015 with follow-up through 2019 in the Veterans Health Administration. We defined biochemical recurrence (BCR) as a prostate-specific antigen ≥0.2 ng/mL. We used a validated natural language processing encoded dataset to identify incident metastatic prostate cancer. We estimated overall survival from time of surgery, time of BCR, and time of first metastasis using the Kaplan-Meier method. We then estimated time from surgery to BCR, BCR to metastatic disease, and prostate-cancer-specific survival from various time points using cumulative incidence considering competing risk of death. RESULTS: Of 21,992 men undergoing radical prostatectomy, we identified 5951 (27%) who developed BCR. Of men with BCR, 677 (11%) developed metastases. We estimated the 10-year cumulative incidence of BCR and metastases after BCR were 28% and 20%, respectively. Median overall survival after BCR was 14years, with 10-year survival of 70%. From the time of metastasis, median overall survival approached 7years, with 10-year overall survival of 34%. Prostate cancer-specific survival for the entire cohort at 10years was 94%. CONCLUSION: In this large contemporary national cohort, survival for men with biochemically recurrent prostate cancer is longer than historical cohorts. When counseling patients and designing clinical studies, these updated estimates may serve as more reliable reflections of current outcomes.

A Phase II Study of Optimized Individualized Adaptive Radiotherapy for Hepatocellular Carcinoma.

PURPOSE: We hypothesized that optimizing the utility of stereotactic body radiotherapy (SBRT) based on the individual patient's probability for tumor control and risk of liver injury would decrease toxicity without sacrificing local control in patients with impaired liver function or tumors not amenable to thermal ablation. PATIENTS AND METHODS: Patients with Child-Pugh (CP) A to B7 liver function with aggregate tumor size >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an Institutional Review Board-approved phase II clinical trial to undergo SBRT with baseline and midtreatment dose optimization using a quantitative, individualized utility-based analysis. Primary endpoints were change in CP score of ≥2 points within 6 months and local control. Protocol-treated patients were compared with patients receiving conventional SBRT at another cancer center using overlap weighting. RESULTS: A total of 56 patients with 80 treated tumors were analyzed with a median follow-up of 11.2 months. Two-year cumulative incidence of local progression was 6.4% [95% confidence interval (CI, 2.4-13.4)]. Twenty-one percent of patients experienced treatment-related toxicity within 6 months, which is similar to the rate for SBRT in patients with CP A liver function. An analysis using overlap weighting revealed similar local control [HR, 0.69; 95% CI (0.25-1.91); P = 0.48] and decreased toxicity [OR, 0.26; 95% CI (0.07-0.99); P = 0.048] compared with conventional SBRT. CONCLUSIONS: Treatment of individuals with impaired liver function or tumors not amenable to thermal ablation with a treatment paradigm designed to optimize utility may decrease treatment-related toxicity while maintaining tumor control.

Flow-Sizing Critical Care Resources.

OBJECTIVES: To describe the factors affecting critical care capacity and how critical care organizations (CCOs) within academic centers in the U.S. flow-size critical care resources under normal operations, strain, and surge conditions. DATA SOURCES: PubMed, federal agency and American Hospital Association reports, and previous CCO survey results were reviewed. STUDY SELECTION: Studies and reports of critical care bed capacity and utilization within CCOs and in the United States were selected. DATA EXTRACTION: The Academic Leaders in the Critical Care Medicine Task Force established regular conference calls to reach a consensus on the approach of CCOs to "flow-sizing" critical care services. DATA SYNTHESIS: The approach of CCOs to "flow-sizing" critical care is outlined. The vertical (relation to institutional resources, e.g., space allocation, equipment, personnel redistribution) and horizontal (interdepartmental, e.g., emergency department, operating room, inpatient floors) integration of critical care delivery (ICUs, rapid response) for healthcare organizations and the methods by which CCOs flow-size critical care during normal operations, strain, and surge conditions are described. The advantages, barriers, and recommendations for the rapid and efficient scaling of critical care operations via a CCO structure are explained. Comprehensive guidance and resources for the development of "flow-sizing" capability by a CCO within a healthcare organization are provided. CONCLUSIONS: We identified and summarized the fundamental principles affecting critical care capacity. The taskforce highlighted the advantages of the CCO governance model to achieve rapid and cost-effective "flow-sizing" of critical care services and provide recommendations and resources to facilitate this capability. The relevance of a comprehensive approach to "flow-sizing" has become particularly relevant in the wake of the latest COVID-19 pandemic. In light of the growing risks of another extreme epidemic, planning for adequate capacity to confront the next critical care crisis is urgent.

On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.

BACKGROUND: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year. RESULTS: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality. CONCLUSIONS: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.

Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study.

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217.

Outcomes after definitive radiation therapy for localized prostate cancer in a national health care delivery system.

PURPOSE: Accurate information regarding real-world outcomes after contemporary radiation therapy for localized prostate cancer is important for shared decision-making. Clinically relevant end points at 10 years among men treated within a national health care delivery system were examined. METHODS: National administrative, cancer registry, and electronic health record data were used for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy within the Veterans Health Administration from 2005 to 2015. National Death Index data were used through 2019 for overall and prostate cancer-specific survival and identified date of incident metastatic prostate cancer using a validated natural language processing algorithm. Metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods were estimated. RESULTS: Among 41,735 men treated with definitive radiation therapy, the median age at diagnosis was 65 years and median follow-up was 8.7 years. Most had intermediate (42%) and high-risk (33%) disease, with 40% receiving androgen deprivation therapy as part of initial therapy. Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low-, intermediate-, and high-risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low-, intermediate-, and high-risk disease. The unadjusted overall survival was lower across increasing disease risk categories at 77%, 71%, and 62% for low-, intermediate-, and high-risk disease (p < .001). CONCLUSIONS: These data provide population-based 10-year benchmarks for clinically relevant end points, including metastasis-free survival, among patients with localized prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high-risk disease in particular suggest that outcomes have recently improved.

The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.

OBJECTIVES: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes. RESULTS: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86). CONCLUSIONS: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.

Advances in Radiation Therapy for Primary Liver Cancer.

During the past 30 years, several advances have been made allowing for safer and more effective treatment of patients with liver cancer. This report reviews recent advances in radiation therapy for primary liver cancers including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. First, studies focusing on liver stereotactic body radiation therapy (SBRT) are reviewed focusing on lessons learned and knowledge gained from early pioneering trials. Then, new technologies to enhance SBRT treatments are explored including adaptive therapy and MRI-guided and biology-guided radiation therapy. Finally, treatment with Y-90 transarterial radioembolization is reviewed with a focus on novel approaches focused on personalized therapy.

Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding.

BACKGROUND: Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants. METHODS: Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer. RESULTS: Thirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; P<0.0001). Breast milk fed infants acquired mucosal anti-spike IgG antibodies (in the nose) only if their mothers were vaccinated antepartum (89% Antepartum; 0% Postpartum; P<0.0001). None of the infants in either group had anti-spike IgA in the blood. Surprisingly, 33% of the infants whose mothers were vaccinated antepartum had high titer anti-spike IgA in the nose (33% Antepartum; 0% Postpartum; P = 0.03). Half-life of maternally transferred plasma IgG antibodies in the Antepartum infant cohort was ~70 days. CONCLUSION: Vaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants.

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies.

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR-positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

Cardiac and Pulmonary Dosimetric Parameters in Patients With Lung Cancer Undergoing Postoperative Radiation Therapy Across a Statewide Consortium.

PURPOSE: The recently published Lung Adjuvant Radiotherapy Trial (Lung ART) reported increased rates of cardiac and pulmonary toxic effects in the postoperative radiation therapy (PORT) arm. It remains unknown whether the dosimetric parameters reported in Lung ART are representative of contemporary real-world practice, which remains relevant for patients undergoing PORT for positive surgical margins. The purpose of this study was to examine heart and lung dose exposure in patients receiving PORT for non-small cell lung cancer across a statewide consortium. METHODS AND MATERIALS: From 2012 to 2022, demographic and dosimetric data were prospectively collected for 377 patients at 27 academic and community centers within the Michigan Radiation Oncology Quality Consortium undergoing PORT for nonmetastatic non-small cell lung cancer. Dosimetric parameters for target coverage and organ-at-risk exposure were calculated using data from dose-volume histograms, and rates of 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) utilization were assessed. RESULTS: Fifty-one percent of patients in this cohort had N2 disease at the time of surgery, and 25% had a positive margin. Sixty-six percent of patients were treated with IMRT compared with 32% with 3D-CRT. The planning target volume was significantly smaller in patients treated with 3D-CRT (149.2 vs 265.4 cm3; P < .0001). The median mean heart dose for all patients was 8.7 Gy (interquartile range [IQR], 3.5-15.3 Gy), the median heart volume receiving at least 5 Gy (V5) was 35.2% (IQR, 18.5%-60.2%), and the median heart volume receiving at least 35 Gy (V35) was 9% (IQR, 3.2%-17.7%). The median mean lung dose was 11.4 Gy (IQR, 8.1-14.3 Gy), and the median lung volume receiving at least 20 Gy (V20) was 19.6% (IQR, 12.7%-25.4%). These dosimetric parameters did not significantly differ by treatment modality (IMRT vs 3D-CRT) or in patients with positive versus negative surgical margins. CONCLUSIONS: With increased rates of IMRT use, cardiac and lung dosimetric parameters in this statewide consortium were slightly lower than those reported in Lung ART. These data provide useful benchmarks for treatment planning in patients undergoing PORT for positive surgical margins.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Cannabis Use in Patients Seen in an Academic Radiation Oncology Department.

PURPOSE: Cannabis use rates are increasing in the United States. Patients with cancer use cannabis for many reasons, even without high-quality supporting data. This study sought to characterize cannabis use among patients seen in radiation oncology in a state that has legalized adult nonmedical use cannabis and to identify key cannabis-related educational topics. METHODS AND MATERIALS: Cannabis history was documented by providers using a structured template at patient visits in an academic radiation oncology practice October 2020 to November 2021. Cannabis use data, including recency/frequency of use, reason, and mode of administration, were summarized, and logistic regression was used to explore associations between patient and disease characteristics and recent cannabis use. A multivariable model employed stepwise variable selection using the Akaike Information Criterion. RESULTS: Of 3143 patients total, 91 (2.9%) declined to answer cannabis use questions, and 343 (10.9%) endorsed recent use (≤1 month ago), 235 (7.5%) noted nonrecent use (>1 month ago), and 2474 (78.7%) denied history of cannabis use. In multivariable analyses, those ≥50 years old (odds ratio [OR], 0.409; 95% confidence interval [CI], 0.294-0.568; P < .001) or with history of prior courses of radiation (OR, 0.748; 95% CI, 0.572-0.979; P = .034) were less likely, and those with a mental health diagnosis not related to substance use (OR, 1.533; 95% CI, 1.171-2.005; P = .002) or who smoked tobacco (OR, 3.003; 95% CI, 2.098-4.299; P < .001) were more likely to endorse recent cannabis use. Patients reported pain, insomnia, and anxiety as the most common reasons for use. Smoking was the most common mode of administration. CONCLUSIONS: Patients are willing to discuss cannabis use with providers and reported recent cannabis use for a variety of reasons. Younger patients new to oncologic care and those with a history of mental illness or tobacco smoking may benefit most from discussions about cannabis given higher rates of cannabis use in these groups.

A descriptive evaluation of causes of death in venovenous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become an important support modality for patients with acute respiratory failure refractory to optimal medical therapy, such as low tidal volume mechanical ventilator support, early paralytic infusion, and early prone positioning. The objective of this cohort study was to investigate the causes and timing of in-hospital mortality in patients on VV ECMO. All patients, excluding trauma and bridge to lung transplant, admitted 8/2014-6/2019 to a specialty ICU for VV ECMO were reviewed. Two hundred twenty-five patients were included. In-hospital mortality was 24.4% (n = 55). Most non-survivors (46/55, 84%) died prior to lung recovery and decannulation from VV ECMO. Most common cause of death (COD) for patients who died on VV ECMO was removal of life sustaining therapy (LST) in setting of multisystem organ failure (MSOF) (n = 24). Nine patients died a median of 9 days [6, 11] after decannulation. Most common COD in these patients was palliative withdrawal of LST due to poor prognosis (n = 3). Non-survivors were older and had worse predictive mortality scores than survivors. We found that death in patients supported with VV ECMO in our study most often occurs prior to decannulation and lung recovery. This study demonstrated that the most common cause of death in patients supported with VV ECMO was removal of LST due MSOF. Acute hemorrhage (systemic or intracranial) was not found to be a common cause of death in our patient population.

SARS-CoV-2 infection and persistence in the human body and brain at autopsy.

Coronavirus disease 2019 (COVID-19) is known to cause multi-organ dysfunction1-3 during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some patients experiencing prolonged symptoms, termed post-acute sequelae of SARS-CoV-2 (refs. 4,5). However, the burden of infection outside the respiratory tract and time to viral clearance are not well characterized, particularly in the brain3,6-14. Here we carried out complete autopsies on 44 patients who died with COVID-19, with extensive sampling of the central nervous system in 11 of these patients, to map and quantify the distribution, replication and cell-type specificity of SARS-CoV-2 across the human body, including the brain, from acute infection to more than seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, predominantly among patients who died with severe COVID-19, and that virus replication is present in multiple respiratory and non-respiratory tissues, including the brain, early in infection. Further, we detected persistent SARS-CoV-2 RNA in multiple anatomic sites, including throughout the brain, as late as 230 days following symptom onset in one case. Despite extensive distribution of SARS-CoV-2 RNA throughout the body, we observed little evidence of inflammation or direct viral cytopathology outside the respiratory tract. Our data indicate that in some patients SARS-CoV-2 can cause systemic infection and persist in the body for months.