Showing papers by "Beaumont Health published in 2021"

COVID-19 vaccine hesitancy among medical students.

Abstract: BACKGROUND: Medical students are among the group of frontline healthcare providers likely to be exposed to COVID-19 patients. It is important to achieve high COVID-19 vaccination coverage rates in this group as soon as a vaccine is available. As future healthcare providers, they will be entrusted with providing vaccine recommendations and counseling vaccine-hesitant patients. METHODS: This project used self-report to assess vaccine hesitancy and acceptance among medical students towards the novel COVID-19 vaccine. RESULTS: Nearly all participants had positive attitudes towards vaccines and agreed they would likely be exposed to COVID-19; however, only 53% indicated they would participate in a COVID-19 vaccine trial and 23% were unwilling to take a COVID-19 vaccine immediately upon FDA approval. Students willing to immediately take the vaccine were more likely to trust public health experts, have fewer concerns about side effects and agree with vaccine mandates (P < 0.05). Concern for serious side effects was independently predictive of lower odds of intent to participate in a COVID-19 vaccine trial (AOR = 0.41, P = 0.01). CONCLUSION: This is the first study to evaluate COVID-19 vaccine hesitancy among US medical students and highlights the need for an educational curriculum about the safety and effectiveness to promote uptake of the COVID-19 vaccine.

Association of anticoagulation dose and survival in hospitalized COVID-19 patients: A retrospective propensity score-weighted analysis.

Abstract: Background Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear. Objectives We evaluated the impact on survival of different AC doses in COVID-19 patients. Methods Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020. Results A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects. Conclusions Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted.

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson’s Disease

Abstract: The gut microbiome can impact brain health and is altered in Parkinson's disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations. We investigated the changes in the functional microbiota in the appendix of PD patients relative to controls (n = 12 PD, 16 C) by metatranscriptomic analysis. We found microbial dysbiosis affecting lipid metabolism, including an upregulation of bacteria responsible for secondary bile acid synthesis. We then quantitatively measure changes in bile acid abundance in PD relative to the controls in the appendix (n = 15 PD, 12 C) and ileum (n = 20 PD, 20 C). Bile acid analysis in the PD appendix reveals an increase in hydrophobic and secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA). Further proteomic and transcriptomic analysis in the appendix and ileum corroborated these findings, highlighting changes in the PD gut that are consistent with a disruption in bile acid control, including alterations in mediators of cholesterol homeostasis and lipid metabolism. Microbially derived toxic bile acids are heightened in PD, which suggests biliary abnormalities may play a role in PD pathogenesis.

Coronavirus Disease 2019 (COVID-19) Seropositivity and Asymptomatic Rates in Healthcare Workers Are Associated with Job Function and Masking.

Abstract: Background Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. Methods An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. Results A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive individuals, 44% reported that they were asymptomatic during the month prior to blood collection. Healthcare roles such as phlebotomy, respiratory therapy, and nursing/nursing support exhibited significantly higher seropositivity. Among participants reporting direct exposure to a Coronavirus Disease 2019 (COVID-19) positive individual, those wearing an N95/PAPR mask had a significantly lower seropositivity rate (10.2%) compared to surgical/other masks (13.1%) or no mask (17.5%). Conclusions Direct contact with COVID-19 patients increased the likelihood of seropositivity among employees but study participants who wore a mask during COVID-19 exposures were less likely to be seropositive. Additionally, a large proportion of seropositive employees self-reported as asymptomatic. (Funded by Beaumont Health and by major donors through the Beaumont Health Foundation). Clinicaltrials.gov number NCT04349202.

Vaccination reduces need for emergency care in breakthrough COVID-19 infections: A multicenter cohort study.

Abstract: Background: While recent literature has shown the efficacy of the SARS-CoV-2 vaccine in preventing infection, it's impact on need for emergency care/hospitalization in breakthrough infections remain unclear, particularly in regions with a high rate of variant viral strains. We aimed to determine if vaccination reduces hospital visits in breakthrough COVID-19. Methods: This observational cohort analysis compared unvaccinated (UV), partially vaccinated (PV), and fully vaccinated (FV) adult patients with SARS-CoV-2 infection requiring emergency care(EC)/hospitalization within an eight-hospital system in Michigan. Demographic and clinical variables were obtained from the electronic record. Vaccination data was obtained from the Michigan Care Improvement Registry and Centers for Disease Control vaccine tracker. Primary endpoint was rate of emergency care/hospitalization encounters among patients diagnosed with COVID-19. Secondary outcome was severe disease-composite outcome (ICU, mechanical ventilation, or in-hospital death). Findings: Between December 15,2020 and April 30,2021, 11,834 EC encounters were included:10,880 (91.9%) UV, 825 (7%) PV, 129 (1.1%) FV. Average age was 53.0 ± 18.2 and 52.8% were female. Accounting for the SARS-CoV-2 vaccination population groups in Michigan, the ED encounters/hospitalizations rate relevant to COVID-19 was 96% lower in FV versus UV (multiplicative effect:0.04, 95% CI 0.03 to 0.06, p < 0.001) in negative binomial regression. COVID-19 EC visits rate peaked at 22.61, 12.88, and 1.29 visits per 100000 for the UV, PV, and FV groups, respectively. In the propensity-score matching weights analysis, FV had a lower risk of composite disease compared to UV but statistically insignificant (HR 0.84, 95% CI 0.52 to 1.38). Interpretation: The need for emergency care/hospitalization due to breakthrough COVID-19 is an exceedingly rare event in fully vaccinated patients. As vaccination has increased regionally, EC visits amongst fully vaccinated individuals have remained low and occur much less frequently than unvaccinated individuals. If hospital-based treatment is required, elderly patients with significant comorbidities are at high-risk for severe outcomes regardless of vaccination status.

Dental students' attitudes and hesitancy toward COVID-19 vaccine.

Abstract: BACKGROUND: Dentists are a group of providers who have been identified by CDC at high risk of exposure to COVID-19 through their contact with patients. This would apply to dental students as well. Thus, it is important to achieve high COVID-19 vaccination rates in this group. Further, as healthcare providers, they are entrusted with providing health recommendations and advocating for their patients, community, and profession, including vaccinations. METHODS: Using ualtricsXM an online platform, in 2020, a survey was administered anonymously to dental students at three dental schools to assess the attitudes of dental students to the novel COVID-19 vaccine. Factors and reasons associated with vaccine hesitancy and acceptance toward the COVID-19 vaccine and likelihood of recommending and giving the vaccination to patients were assessed. RESULTS: Nearly, all participants had positive attitudes toward vaccines in general, agreed they would likely be exposed to COVID-19, and personally knew someone who had COVID-19; however, only 56% are willing to take a COVID-19 vaccine as soon as an FDA-approved vaccine was available. Of those unwilling to take the vaccine, 63% reported they would take it if mandated by the health systems/dental school; however, 16.3% of the overall respondents would not take the COVID-19 vaccine even if mandated. Several factors are associated with vaccine acceptance and the likelihood of recommending the vaccination, such as trusting public health experts, concerns about side effects, and agreeing with vaccine mandates. CONCLUSION: Our results highlight the need for an educational curriculum about the safety and effectiveness to promote the uptake of COVID-19 vaccine.

External Validation of a Clinical Risk Score to Predict Hospital Admission and In-Hospital Mortality in COVID-19 Patients

Abstract: Identification of patients with novel coronavirus disease 2019 (COVID-19) requiring hospital admission or at high-risk of in-hospital mortality is essential to guide patient triage and to provide t...

Machine learning methods to predict mechanical ventilation and mortality in patients with COVID-19.

Abstract: BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has affected millions of people across the globe. It is associated with a high mortality rate and has created a global crisis by straining medical resources worldwide. OBJECTIVES: To develop and validate machine-learning models for prediction of mechanical ventilation (MV) for patients presenting to emergency room and for prediction of in-hospital mortality once a patient is admitted. METHODS: Two cohorts were used for the two different aims. 1980 COVID-19 patients were enrolled for the aim of prediction ofMV. 1036 patients' data, including demographics, past smoking and drinking history, past medical history and vital signs at emergency room (ER), laboratory values, and treatments were collected for training and 674 patients were enrolled for validation using XGBoost algorithm. For the second aim to predict in-hospital mortality, 3491 hospitalized patients via ER were enrolled. CatBoost, a new gradient-boosting algorithm was applied for training and validation of the cohort. RESULTS: Older age, higher temperature, increased respiratory rate (RR) and a lower oxygen saturation (SpO2) from the first set of vital signs were associated with an increased risk of MV amongst the 1980 patients in the ER. The model had a high accuracy of 86.2% and a negative predictive value (NPV) of 87.8%. While, patients who required MV, had a higher RR, Body mass index (BMI) and longer length of stay in the hospital were the major features associated with in-hospital mortality. The second model had a high accuracy of 80% with NPV of 81.6%. CONCLUSION: Machine learning models using XGBoost and catBoost algorithms can predict need for mechanical ventilation and mortality with a very high accuracy in COVID-19 patients.

Omission of Axillary Lymph Node Dissection is Associated with Inferior Survival in Breast Cancer Patients with Residual N1 Nodal Disease Following Neoadjuvant Chemotherapy

Abstract: The appropriateness of substituting sentinel lymph node dissection (SLND) and regional nodal irradiation (RNI) for axillary lymph node dissection (ALND) in patients with residual lymph node (LN) disease following neoadjuvant chemotherapy (NAC) is unknown. We used the National Cancer Database (NCDB) to compare survival following SLND and ALND in breast cancer patients with residual LN disease. We analyzed NCDB patients, treated between 2006 and 2014, with cT1–3, cN1, cM0 breast cancer and residual disease in 1–3 axillary LNs (ypN1) following NAC. Patients were grouped into those who received SLND (defined as removal of ≤ 4 LNs) and RNI, or ALND and RNI. Patients were matched for all patient, tumor, and treatment characteristics. We identified 1313 eligible patients in the ALND group and 304 patients in the SLND group. For the matched cohorts, SLND was associated with significantly lower survival in both univariate and doubly robust multivariable analyses (MVA) (HR 1.7, 95% CI 1.3–2.2, P < 0.001 for MVA), with estimated 5-year OS of 71%, compared with 77% in the ALND group (P = 0.01). Exploratory subgroup analyses showed that SLND was comparable with ALND in patients with luminal A or B tumors with a single metastatic LN (HR 1.03, 95% CI 0.59–1.8, (P = 0.91). Our analysis suggests that, while an ALND may not be needed for patients with limited residual nodal burden and biologically favorable tumors, SLND should not be routinely substituted for ALND in patients with ypN1 disease following NAC until its efficacy is confirmed by prospective trials.

Adjuvant PARP Inhibitors in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update

Abstract: ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.

Proton Therapy for Breast Cancer: A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee.

Abstract: Radiation therapy plays an important role in the multidisciplinary management of breast cancer Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs Proton therapy reduces the dose to nontarget structures while optimizing target coverage However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research

Cardiorespiratory Fitness, Inflammation, and the Incident Risk of Pneumonia.

Abstract: Introduction Both inflammation and cardiorespiratory fitness (CRF) are associated with the risk of respiratory infections. To clarify the hypothesis that CRF attenuates the incident risk of pneumonia due to inflammation, we conducted a prospective study examining the independent and joint associations of inflammation and CRF on the risk of pneumonia in a population sample of 2041 middle-aged men. Methods Cardiorespiratory fitness was directly measured as peak oxygen uptake (V˙O2peak) during progressive exercise testing to volitional fatigue, and categorized into tertiles. Inflammation was defined by high-sensitivity C-reactive protein (hsCRP). Pneumonia cases were identified by internal medicine physicians using the International Classification of Diseases codes in clinical practice. Results During a median follow-up of 27 yr, 432 pneumonia cases were recorded. High hsCRP and CRF were associated with a higher risk (HR = 1.38; 95% CI, 1.02-1.88) and a lower risk of pneumonia (HR = 0.55; CI, 0.39-0.76) after adjusting for potential confounders, respectively. Compared with normal hsCRP-Fit, moderate to high hsCRP-Unfit had an increased risk of pneumonia (HR = 1.63; CI, 1.21-2.20), but moderate to high hsCRP-Fit was not associated with an increased risk of pneumonia (HR = 1.25; CI, 0.93-1.68). Conclusions High CRF attenuates the increased risk of pneumonia due to inflammation. These findings have potential implications for the prevention of respiratory infection characterized by systemic inflammation, such as coronavirus disease-2019 (COVID-19).

Reclassification of prosthesis-patient mismatch after transcatheter aortic valve replacement using predicted vs. measured indexed effective orifice area.

Abstract: AIMS The objective was to compare the incidence and impact on outcomes of measured (PPMM) vs. predicted (PPMP) prosthesis-patient mismatch following transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS All consecutives patients who underwent TAVR between 2007 and 2018 were included. Effective orifice area (EOA) was measured by Doppler-echocardiography using the continuity equation and predicted according to the normal reference for each model and size of valve. PPM was defined using EOA indexed (EOAi) to body surface area as moderate if ≤0.85 cm2/m2 and severe if ≤ 0.65 cm2/m2 (respectively, ≤ 0.70 and ≤ 0.55 cm2/m2 if body mass index ≥ 30 kg/m2). The outcome endpoints were high residual gradient (≥20 mmHg) and the composite of cardiovascular mortality and hospital readmission for heart failure at 1 year. Overall, 1088 patients underwent a TAVR (55% male, age 79.1 ± 8.4 years, and STS score 6.6 ± 4.7%); balloon-expandable device was used in 83%. Incidence of moderate (10% vs. 27%) and severe (1% vs. 17%) PPM was markedly lower when defined by predicted vs. measured EOAi (P < 0.001). Balloon-expandable device implantation (OR: 1.90, P = 0.029) and valve-in-valve procedure (n = 118; OR: 3.21, P < 0.001) were the main factors associated with PPM occurrence. Compared with measured PPM, predicted PPM showed stronger association with high residual gradient. Severe measured or predicted PPM was not associated with clinical outcomes. CONCLUSION The utilization of the predicted EOAi reclassifies the majority of patients with PPM to no PPM following TAVR. Compared with measured PPM, predicted PPM had stronger association with haemodynamic outcomes, while both methods were not associated with clinical outcomes.

Timing of corticosteroids impacts mortality in hospitalized COVID-19 patients.

Abstract: The optimal timing of initiating corticosteroid treatment in hospitalized patients is unknown. We aimed to assess the relationship between timing of initial corticosteroid treatment and in-hospital mortality in COVID-19 patients. In this observational study through medical record analysis, we quantified the mortality benefit of corticosteroids in two equally matched groups of hospitalized COVID-19 patients. We subsequently evaluated the timing of initiating corticosteroids and its effect on mortality in all patients receiving corticosteroids. Demographic, clinical, and laboratory variables were collected and employed for multivariable regression analyses. 1461 hospitalized patients with confirmed COVID-19 were analyzed. Of these, 760 were also matched into two equal groups based on having received corticosteroid therapy. Patients receiving corticosteroids had a lower risk of death than those who did not (HR 0.67, 95% CI 0.67–0.90; p = 0.01). Timing of corticosteroids was assessed for all 615 patients receiving corticosteroids during admission. Patients receiving first dose of corticosteroids > 72 h into hospitalization had a lower risk of death compared to patients with first dose at earlier time intervals (HR 0.56, 95% CI 0.38–0.82; p = 0.003). There was a mortality benefit in patients with > 7 days of symptom onset to initiation of corticosteroids (HR 0.56, 95% CI 0.33–0.95; p = 0.03). In patients receiving oxygen therapy, corticosteroids reduced risk of death in mechanically ventilated patients (HR 0.38, 95% CI 0.24–0.60; p 7 days should trigger initiation of corticosteroids. In the absence of invasive mechanical ventilation, corticosteroids should be initiated if the patient remains hospitalized at 72 h. Hypoxia requiring supplemental oxygen therapy should not be a trigger for initiation of corticosteroids unless the timing is appropriate.

Race, Ethnicity, Neighborhood Characteristics, and In-Hospital Coronavirus Disease-2019 Mortality.

Abstract: Background Despite many studies reporting disparities in coronavirus disease-2019 (COVID-19) incidence and outcomes in Black and Hispanic/Latino populations, mechanisms are not fully understood to inform mitigation strategies. Objective The aim was to test whether neighborhood factors beyond individual patient-level factors are associated with in-hospital mortality from COVID-19. We hypothesized that the Area Deprivation Index (ADI), a neighborhood census-block-level composite measure, was associated with COVID-19 mortality independently of race, ethnicity, and other patient factors. Research design Multicenter retrospective cohort study examining COVID-19 in-hospital mortality. Subjects Inclusion required hospitalization with positive SARS-CoV-2 test or COVID-19 diagnosis at three large Midwestern academic centers. Measures The primary study outcome was COVID-19 in-hospital mortality. Patient-level predictors included age, sex, race, insurance, body mass index, comorbidities, and ventilation. Neighborhoods were examined through the national ADI neighborhood deprivation rank comparing in-hospital mortality across ADI quintiles. Analyses used multivariable logistic regression with fixed site effects. Results Among 5999 COVID-19 patients median age was 61 (interquartile range: 44-73), 48% were male, 30% Black, and 10.8% died. Among patients who died, 32% lived in the most disadvantaged quintile while 11% lived in the least disadvantaged quintile; 52% of Black, 24% of Hispanic/Latino, and 8.5% of White patients lived in the most disadvantaged neighborhoods.Living in the most disadvantaged neighborhood quintile predicted higher mortality (adjusted odds ratio: 1.74; 95% confidence interval: 1.13-2.67) independent of race. Age, male sex, Medicare coverage, and ventilation also predicted mortality. Conclusions Neighborhood disadvantage independently predicted in-hospital COVID-19 mortality. Findings support calls to consider neighborhood measures for vaccine distribution and policies to mitigate disparities.

Lipid Profiling of Alzheimer's Disease Brain Highlights Enrichment in Glycerol(phospho)lipid, and Sphingolipid Metabolism.

Abstract: Alzheimer’s disease (AD) is reported to be closely linked with abnormal lipid metabolism. To gain a more comprehensive understanding of what causes AD and its subsequent development, we profiled the lipidome of postmortem (PM) human brains (neocortex) of people with a range of AD pathology (Braak 0–6). Using high-resolution mass spectrometry, we employed a semi-targeted, fully quantitative lipidomics profiling method (Lipidyzer) to compare the biochemical profiles of brain tissues from persons with mild AD (n = 15) and severe AD (AD; n = 16), and compared them with age-matched, cognitively normal controls (n = 16). Univariate analysis revealed that the concentrations of 420 lipid metabolites significantly (p < 0.05; q < 0.05) differed between AD and controls. A total of 49 lipid metabolites differed between mild AD and controls, and 439 differed between severe AD and mild AD. Interestingly, 13 different subclasses of lipids were significantly perturbed, including neutral lipids, glycerolipids, glycerophospholipids, and sphingolipids. Diacylglycerol (DAG) (14:0/14:0), triacylglycerol (TAG) (58:10/FA20:5), and TAG (48:4/FA18:3) were the most notably altered lipids when AD and control brains were compared (p < 0.05). When we compare mild AD and control brains, phosphatidylethanolamine (PE) (p-18:0/18:1), phosphatidylserine (PS) (18:1/18:2), and PS (14:0/22:6) differed the most (p < 0.05). PE (p-18:0/18:1), DAG (14:0/14:0), and PS (18:1/20:4) were identified as the most significantly perturbed lipids when AD and mild AD brains were compared (p < 0.05). Our analysis provides the most extensive lipid profiling yet undertaken in AD brain tissue and reveals the cumulative perturbation of several lipid pathways with progressive disease pathology. Lipidomics has considerable potential for studying AD etiology and identifying early diagnostic biomarkers.

Treatment of WHO Grade 2 Meningiomas With Stereotactic Radiosurgery: Identification of an Optimal Group for SRS Using RPA.

Abstract: Purpose This study assesses a large multi-institutional database to present the outcomes of World Health Organization grade 2 meningiomas treated with stereotactic radiosurgery (SRS). We also compare the 3-year progression-free survival (PFS) to that reported in the Radiation Therapy Oncology Group 0539 phase 2 cooperative group meningioma trial. Methods and Materials From an international, multicenter group, data were collected for grade 2 meningioma patients treated with SRS for demonstrable tumor from 1994 to 2019. Statistical methods used included the Kaplan-Meier method, Cox proportional hazards analysis, and recursive partitioning analysis. Results Two hundred thirty-three patients treated at 12 institutions were included. Patients presented at a median age of 60 years (range, 13-90), and many had at least 2 prior resections (30%) or radiation therapy (22%). Forty-eight percent of patients had prior gross total resection. At SRS, the median treatment volume was 6.1 cm3 (0.1-97.6). A median 15 Gy (10-30) was delivered to a median percent isodose of 50 (30-80), most commonly in 1 fraction (95%). A model was developed using recursive partitioning analysis, with one point attributed to age >50 years, treatment volume >11.5 cm3, and prior radiation therapy or multiple surgeries. The good-prognostic group (score, 0-1) had improved PFS (P 50 years (hazard ratio = 1.85 [95% confidence interval, 1.09-3.14]) and multiple prior surgeries (hazard ratio = 1.80 [1.09-2.99]) also portended reduced PFS in patients without prior radiation therapy. Two hundred eighteen of 233 patients in this study qualified for the high-risk group of Radiation Therapy Oncology Group 0539, and they demonstrated similar outcomes (3-year PFS: 53.9% vs 58.8%). The good-prognostic group of SRS patients demonstrated slightly improved outcomes (3-year PFS: 63.1% vs 58.8%). Conclusions SRS should be considered in carefully selected patients with atypical meningiomas. We suggest the use of our good-prognostic group to optimize patient selection, and we strongly encourage the initiation of a clinical trial to prospectively validate these outcomes.

Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer's Disease.

Abstract: There is an extensive literature relating to factors associated with the development of Alzheimer's disease (AD), but less is known about factors which may contribute to its progression. This review examined the literature with regard to 15 factors which were suggested by PubMed search to be positively associated with the cognitive and/or neuropathological progression of AD. The factors were grouped as potentially modifiable (vascular risk factors, comorbidities, malnutrition, educational level, inflammation, and oxidative stress), non-modifiable (age at clinical onset, family history of dementia, gender, Apolipoprotein E ɛ4, genetic variants, and altered gene regulation), and clinical (baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs). Although conflicting results were found for the majority of factors, a positive association was found in nearly all studies which investigated the relationship of six factors to AD progression: malnutrition, genetic variants, altered gene regulation, baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs. Whether these or other factors which have been suggested to be associated with AD progression actually influence the rate of decline of AD patients is unclear. Therapeutic approaches which include addressing of modifiable factors associated with AD progression should be considered.

One-year outcomes of supersaturated oxygen therapy in acute anterior myocardial infarction: The IC-HOT study

Abstract: Background Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. Objectives To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. Methods IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. Results Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. Conclusions Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.

Inhibition of Colony-Stimulating Factor-1 Receptor Enhances the Efficacy of Radiotherapy and Reduces Immune Suppression in Glioblastoma.

Abstract: Aim To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy of radiotherapy in glioblastoma (GBM). Materials and methods The CSF-1R inhibitor BLZ-945 was used to examine the impact of CSF-1R inhibition on M2 polarization in vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945. Results BLZ-945 reduced M2 polarization in vitro. BLZ-945 alone did not improve median overall survival (mOS=29 days) compared to control mice (mOS=27 days). RT improved survival (mOS=45 days; p=0.02), while RT plus BLZ-945 led to the longest survival (mOS=not reached; p=0.005). Resected tumors had a relatively large population of M2 TAMs in GBM at baseline, which was increased in response to RT. BLZ-945 reduced RT-induced M2 infiltration. Conclusion Inhibition of CSF-1R improved response to RT in the treatment of GBM and may represent a promising strategy to improve RT-induced antitumor immune responses.

Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments 2-22-2021.

Abstract: OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care. METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction score was derived from a 50% random sample (n = 9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables. RESULTS: Multivariable regression yielded a 13-variable score, which was simplified to a 13-point score: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation 75% probability with +5 or more points). CONCLUSION: Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decisions about isolation and testing at high throughput checkpoints.

Feasibility and efficacy of enteral tube feeding on weight stability, lean body mass, and patient-reported outcomes in pancreatic cancer cachexia

Abstract: Background Advanced pancreatic ductal adenocarcinoma (PDAC) is characterized by progressive weight loss and nutritional deterioration. This wasting has been linked to poor survival outcomes, alterations in host defenses, decreased functional ability, and diminished health-related quality of life (HRQOL) in pancreatic cancer patients. There are currently no standardized approaches to the management of pancreatic cancer cachexia. This study explores the feasibility and efficacy of enteral tube feeding of a peptide-based formula to improve weight stability and patient-reported outcomes (PROs) in advanced PDAC patients with cachexia. Methods This was a single-institution, single-arm prospective trial conducted between April 2015 and March 2019. Eligible patients were adults (>18 years) diagnosed with advanced or locally advanced PDAC and cachexia, defined as greater than 5% unexplained weight loss within 6 months from screening. The study intervention included three 28 day cycles of a semi-elemental peptide-based formula, administered through a jejunal or gastrojejunal feeding tube. The primary outcome was weight stability at 3 months (Cycle 3), defined as weight change less than 0.1 kg/baseline BMI unit from baseline. Secondary outcomes included changes in lean body mass, appendicular lean mass, bone mineral density, fat mass, and percent body fat, as measured with a DEXA scan, HRQOL (EORTC QLQC30) and NIH PROMIS PROs assessed at each cycle. Daily activity (steps, distance, active minutes, heart rate, and sleep) were remotely monitored using a wearable activity monitor (Fitbit) over the 3 month study period. Results Thirty-six patients were screened for eligibility, 31 patients consented onto study and underwent jejunal tube placement, and 16 patients completed treatment: mean age 67 years (SD 9.3), 43.8% male. Among evaluable patients (n = 16), weight stability was achieved in 10 patients (62.5%), thus completing the trial early. Increases in lean body mass (1273.1, SD: 4078, P = 0.01) and appendicular lean mass (0.45, SD: 0.6, P = 0.02) were observed. Statistically significant improvements at Cycle 3 from baseline were also observed for QLQC30 role function [mean difference (MD): 20.1, P = 0.03], appetite (MD: 27.4, P = 0.02), and global health scores (MD: 13.3, P = 0.05) as well as for NIH PROMIS t-scores for depression (MD: -10.4, P = 0.006) and pain interference (MD: -7.5, P = 0.05). Objectively monitored (Fitbit) activity levels increased, although statistical significance was not reached. Conclusions Our findings suggest that enteral nutrition support may improve weight stability, lean body mass, appendicular lean mass and PROs in PDAC patients with cachexia who completed treatment, representing a subsample of the study population. The feasibility and role of enteral feeding in routine care remain unclear, and larger and randomized controlled trials are warranted.

Long COVID and COVID-19-associated cystitis (CAC).

Abstract: There is scarce literature regarding genitourinary symptoms in COVID-19, especially post-acute disease otherwise known as Long COVID. We identified recovered COVID-19 patients presenting with new or worsening overactive bladder symptoms, known as COVID-19-associated cystitis (CAC). We used the American Urological Association Urology Care Foundation Overactive Bladder (OAB) Assessment Tool to screen COVID-19 recovered patients presenting with urological complaints at our urban-located institution from 5/22/2020 to 12/31/2020. Patients 10–14 weeks post-discharge responded to 5 symptom and 4 quality-of-life (QoL) questions. We reported median symptom scores, as well as QoL scores, based on new or worsening urinary symptoms, and by sex. We identified 350 patients with de novo or worsening OAB symptoms 10–14 weeks after hospitalization with COVID-19. The median total OAB symptom score in both men and women was 18. The median total QoL score for both men and women was 19. Patients with worsening OAB symptoms had a median pre-COVID-19 symptom score of 8 (4–10) compared to post-COVID-19 median symptom score of 19 (17–21). Median age was 64.5 (range 47–82). Median hospital length-of-stay was 10 days (range 5–30). We report survey-based results of patients suffering from new or worsening OAB symptoms months after their hospitalization from COVID-19. Future studies with larger sample sizes and more extensive testing will hopefully elucidate the specific pathophysiology of OAB symptoms in the context of long COVID so urologists can timely and appropriately treat their patients.

Stereotactic Radiosurgery for Atypical (World Health Organization II) and Anaplastic (World Health Organization III) Meningiomas: Results From a Multicenter, International Cohort Study.

Abstract: BACKGROUND Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described. OBJECTIVE To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs. METHODS An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model. RESULTS A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively. CONCLUSION AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.