Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae.

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are debilitating, clinically heterogeneous and of unknown molecular etiology. A transcriptome-wide investigation was performed in 165 acutely infected hospitalized individuals who were followed clinically into the post-acute period. Distinct gene expression signatures of post-acute sequelae were already present in whole blood during acute infection, with innate and adaptive immune cells implicated in different symptoms. Two clusters of sequelae exhibited divergent plasma-cell-associated gene expression patterns. In one cluster, sequelae associated with higher expression of immunoglobulin-related genes in an anti-spike antibody titer-dependent manner. In the other, sequelae associated independently of these titers with lower expression of immunoglobulin-related genes, indicating lower non-specific antibody production in individuals with these sequelae. This relationship between lower total immunoglobulins and sequelae was validated in an external cohort. Altogether, multiple etiologies of post-acute sequelae were already detectable during SARS-CoV-2 infection, directly linking these sequelae with the acute host response to the virus and providing early insights into their development.

The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.

PURPOSE: To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). METHODS: Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses. RESULTS: Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance. CONCLUSION: Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

Acute COVID-19 gene-expression profiles show multiple etiologies of long-term sequelae.

Two years into the SARS-CoV-2 pandemic, the post-acute sequelae of infection are compounding the global health crisis. Often debilitating, these sequelae are clinically heterogeneous and of unknown molecular etiology. Here, a transcriptome-wide investigation of this new condition was performed in a large cohort of acutely infected patients followed clinically into the post-acute period. Gene expression signatures of post-acute sequelae were already present in whole blood during the acute phase of infection, with both innate and adaptive immune cells involved. Plasma cells stood out as driving at least two distinct clusters of sequelae, one largely dependent on circulating antibodies against the SARS-CoV-2 spike protein and the other antibody-independent. Altogether, multiple etiologies of post-acute sequelae were found concomitant with SARS-CoV-2 infection, directly linking the emergence of these sequelae with the host response to the virus.

Combining Initial Radiographs and Clinical Variables Improves Deep Learning Prognostication in Patients with COVID-19 from the Emergency Department.

PURPOSE: To train a deep learning classification algorithm to predict chest radiograph severity scores and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In this retrospective cohort study, patients aged 21-50 years who presented to the emergency department (ED) of a multicenter urban health system from March 10 to 26, 2020, with COVID-19 confirmation at real-time reverse-transcription polymerase chain reaction screening were identified. The initial chest radiographs, clinical variables, and outcomes, including admission, intubation, and survival, were collected within 30 days (n = 338; median age, 39 years; 210 men). Two fellowship-trained cardiothoracic radiologists examined chest radiographs for opacities and assigned a clinically validated severity score. A deep learning algorithm was trained to predict outcomes on a holdout test set composed of patients with confirmed COVID-19 who presented between March 27 and 29, 2020 (n = 161; median age, 60 years; 98 men) for both younger (age range, 21-50 years; n = 51) and older (age >50 years, n = 110) populations. Bootstrapping was used to compute CIs. RESULTS: The model trained on the chest radiograph severity score produced the following areas under the receiver operating characteristic curves (AUCs): 0.80 (95% CI: 0.73, 0.88) for the chest radiograph severity score, 0.76 (95% CI: 0.68, 0.84) for admission, 0.66 (95% CI: 0.56, 0.75) for intubation, and 0.59 (95% CI: 0.49, 0.69) for death. The model trained on clinical variables produced an AUC of 0.64 (95% CI: 0.55, 0.73) for intubation and an AUC of 0.59 (95% CI: 0.50, 0.68) for death. Combining chest radiography and clinical variables increased the AUC of intubation and death to 0.88 (95% CI: 0.79, 0.96) and 0.82 (95% CI: 0.72, 0.91), respectively. CONCLUSION: The combination of imaging and clinical information improves outcome predictions.Supplemental material is available for this article.© RSNA, 2020.

Coronary artery calcification in COVID-19 patients: an imaging biomarker for adverse clinical outcomes.

BACKGROUND: Recent studies have demonstrated a complex interplay between comorbid cardiovascular disease, COVID-19 pathophysiology, and poor clinical outcomes. Coronary artery calcification (CAC) may therefore aid in risk stratification of COVID-19 patients. METHODS: Non-contrast chest CT studies on 180 COVID-19 patients ≥ age 21 admitted from March 1, 2020 to April 27, 2020 were retrospectively reviewed by two radiologists to determine CAC scores. Following feature selection, multivariable logistic regression was utilized to evaluate the relationship between CAC scores and patient outcomes. RESULTS: The presence of any identified CAC was associated with intubation (AOR: 3.6, CI: 1.4-9.6) and mortality (AOR: 3.2, CI: 1.4-7.9). Severe CAC was independently associated with intubation (AOR: 4.0, CI: 1.3-13) and mortality (AOR: 5.1, CI: 1.9-15). A greater CAC score (UOR: 1.2, CI: 1.02-1.3) and number of vessels with calcium (UOR: 1.3, CI: 1.02-1.6) was associated with mortality. Visualized coronary stent or coronary artery bypass graft surgery (CABG) had no statistically significant association with intubation (AOR: 1.9, CI: 0.4-7.7) or death (AOR: 3.4, CI: 1.0-12). CONCLUSION: COVID-19 patients with any CAC were more likely to require intubation and die than those without CAC. Increasing CAC and number of affected arteries was associated with mortality. Severe CAC was associated with higher intubation risk. Prior CABG or stenting had no association with elevated intubation or death.

Portable Chest Radiography as an Exclusionary Test for Adverse Clinical Outcomes During the COVID-19 Pandemic.

BACKGROUND: Chest radiography (CXR) often is performed in the acute setting to help understand the extent of respiratory disease in patients with COVID-19, but a clearly defined role for negative chest radiograph results in assessing patients has not been described. RESEARCH QUESTION: Is portable CXR an effective exclusionary test for future adverse clinical outcomes in patients suspected of having COVID-19? STUDY DESIGN AND METHODS: Charts of consecutive patients suspected of having COVID-19 at five EDs in New York City between March 19, 2020, and April 23, 2020, were reviewed. Patients were categorized based on absence of findings on initial CXR. The primary outcomes were hospital admission, mechanical ventilation, ARDS, and mortality. RESULTS: Three thousand two hundred forty-five adult patients, 474 (14.6%) with negative initial CXR results, were reviewed. Among all patients, negative initial CXR results were associated with a low probability of future adverse clinical outcomes, with negative likelihood ratios of 0.27 (95% CI, 0.23-0.31) for hospital admission, 0.24 (95% CI, 0.16-0.37) for mechanical ventilation, 0.19 (95% CI, 0.09-0.40) for ARDS, and 0.38 (95% CI, 0.29-0.51) for mortality. Among the subset of 955 patients younger than 65 years and with a duration of symptoms of at least 5 days, no patients with negative CXR results died, and the negative likelihood ratios were 0.17 (95% CI, 0.12-0.25) for hospital admission, 0.09 (95% CI, 0.02-0.36) for mechanical ventilation, and 0.09 (95% CI, 0.01-0.64) for ARDS. INTERPRETATION: Initial CXR in adult patients suspected of having COVID-19 is a strong exclusionary test for hospital admission, mechanical ventilation, ARDS, and mortality. The value of CXR as an exclusionary test for adverse clinical outcomes is highest among young adults, patients with few comorbidities, and those with a prolonged duration of symptoms.

Relationship of hospital volume on outcomes in patients with acute pulmonary embolism: Analysis of a 70,000 patient database.

Positive relationships between volume and outcome have been seen in several surgical and medical conditions, resulting in more centralized and specialized care structures. Currently, there is a scarcity of literature involving the volume-outcome relationship in pulmonary embolism (PE). Using a state-wide dataset that encapsulates all non-federal admissions in New York State, we performed a retrospective cohort study on admitted patients with a diagnosis of PE. A total of 70,443 cases were separated into volume groups stratified by hospital quartile. Continuous and categorical variables were compared between cohorts. Multivariable regression analysis was conducted to assess predictors of 1-year mortality, 30-day all-cause readmission, 30-day PE-related readmission, length of stay, and total charges. Of the 205 facilities that were included, 128 (62%) were labeled low volume, 39 (19%) medium volume, 23 (11%) high volume, and 15 (7%) very high volume. Multivariable analysis showed that very high volume was associated with decreased 30-day PE-related readmission (OR 0.64; 95% CI, 0.55 to 0.73), decreased 30-day all-cause readmission (OR 0.84; 95% CI, 0.79 to 0.89), decreased 1-year mortality (OR 0.85; 95% CI, 0.80 to 0.91), decreased total charges (OR 0.96; 95% CI, 0.94 to 0.98), and decreased length of stay (OR 0.94; 95% CI, 0.92 to 0.96). In summary, facilities with higher volumes of acute PE were found to have less 30-day PE-related readmissions, less all-cause readmissions, shorter length of stay, decreased 1-year mortality, and decreased total charges.

Spontaneous subcutaneous emphysema and pneumomediastinum in non-intubated patients with COVID-19.

PURPOSE: We describe the presenting characteristics and hospital course of 11 novel coronavirus (COVID-19) patients who developed spontaneous subcutaneous emphysema (SE) with or without pneumomediastinum (SPM) in the absence of prior mechanical ventilation. MATERIALS AND METHODS: A total of 11 non-intubated COVID-19 patients (8 male and 3 female, median age 61 years) developed SE and SPM between March 15 and April 30, 2020 at a multi-center urban health system in New York City. Demographics (age, gender, smoking status, comorbid conditions, and body-mass index), clinical variables (temperature, oxygen saturation, and symptoms), and laboratory values (white blood cell count, C-reactive protein, D-dimer, and peak interleukin-6) were collected. Chest radiography (CXR) and computed tomography (CT) were analyzed for SE, SPM, and pneumothorax by a board-certified cardiothoracic-fellowship trained radiologist. RESULTS: Eleven non-intubated patients developed SE, 36% (4/11) of whom had SE on their initial CXR. Concomitant SPM was apparent in 91% (10/11) of patients, and 45% (5/11) also developed pneumothorax. Patients developed SE on average 13.3 days (SD: 6.3) following symptom onset. No patients reported a history of smoking. The most common comorbidities included hypertension (6/11), diabetes mellitus (5/11), asthma (3/11), dyslipidemia (3/11), and renal disease (2/11). Four (36%) patients expired during hospitalization. CONCLUSION: SE and SPM were observed in a cohort of 11 non-intubated COVID-19 patients without any known cause or history of invasive ventilation. Further investigation is required to elucidate the underlying mechanism in this patient population.

Clinical and Chest Radiography Features Determine Patient Outcomes in Young and Middle-aged Adults with COVID-19.

Background Chest radiography has not been validated for its prognostic utility in evaluating patients with coronavirus disease 2019 (COVID-19). Purpose To analyze the prognostic value of a chest radiograph severity scoring system for younger (nonelderly) patients with COVID-19 at initial presentation to the emergency department (ED); outcomes of interest included hospitalization, intubation, prolonged stay, sepsis, and death. Materials and Methods In this retrospective study, patients between the ages of 21 and 50 years who presented to the ED of an urban multicenter health system from March 10 to March 26, 2020, with COVID-19 confirmation on real-time reverse transcriptase polymerase chain reaction were identified. Each patient's ED chest radiograph was divided into six zones and examined for opacities by two cardiothoracic radiologists, and scores were collated into a total concordant lung zone severity score. Clinical and laboratory variables were collected. Multivariable logistic regression was used to evaluate the relationship between clinical parameters, chest radiograph scores, and patient outcomes. Results The study included 338 patients: 210 men (62%), with median age of 39 years (interquartile range, 31-45 years). After adjustment for demographics and comorbidities, independent predictors of hospital admission (n = 145, 43%) were chest radiograph severity score of 2 or more (odds ratio, 6.2; 95% confidence interval [CI]: 3.5, 11; P < .001) and obesity (odds ratio, 2.4 [95% CI: 1.1, 5.4] or morbid obesity). Among patients who were admitted, a chest radiograph score of 3 or more was an independent predictor of intubation (n = 28) (odds ratio, 4.7; 95% CI: 1.8, 13; P = .002) as was hospital site. No significant difference was found in primary outcomes across race and ethnicity or those with a history of tobacco use, asthma, or diabetes mellitus type II. Conclusion For patients aged 21-50 years with coronavirus disease 2019 presenting to the emergency department, a chest radiograph severity score was predictive of risk for hospital admission and intubation. © RSNA, 2020 Online supplemental material is available for this article.

Use of 70- to 150-µm Radiopaque Spherical Embolics for Prostatic Artery Embolization.

This retrospective report describes treatment of 21 patients who underwent prostatic artery embolization using 70- to 150-µm radiopaque microspheres for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Seventeen patients (81%) received successful bilateral prostatic artery embolization. At a mean follow-up of 42 days (range, 25-59 days), patients showed improvement in International Prostate Symptom Score (n = 11; mean = 10.6; P = .001), quality of life score (n = 17; mean = 2.0; P = .02), and International Index of Erectile Function (n = 17; mean = 9.3; P = .01). The mean prostate volume reduction was 28 mL (16.2%; P = .003). Nontarget embolization occurred twice, resulting in 1 minor adverse event of hematospermia.

COVID-19: A Multimodality Review of Radiologic Techniques, Clinical Utility, and Imaging Features.

In this article we will review the imaging features of coronavirus disease 2019 (COVID-19) across multiple modalities, including radiography, CT, MRI, PET/CT, and US. Given that COVID-19 primarily affects the lung parenchyma by causing pneumonia, our directive is to focus on thoracic findings associated with COVID-19. We aim to enhance radiologists' understanding of this disease to help guide diagnosis and management. Supplemental material is available for this article. © RSNA, 2020.

A rare case of hepatocellular carcinoma arising from gadoxetate-retaining hepatic adenoma.

Hepatocellular adenomas (HCAs) are benign lesions of the liver which can rarely undergo malignant transformation. We report a 26-year-old woman with no underlying liver disease found to have an incidental liver lesion on noncontrast CT during workup for gastric reflux. Follow up MRI revealed a 10 cm gadoxetate-retaining lesion within the right hepatic lobe with imaging features suggestive of HCA vs focal nodular hyperplasia . Within this lesion was a focus of arterial enhancement with venous washout suggestive of hepatocellular carcinoma (HCC) within HCA, later confirmed at surgical resection. Understanding the imaging characteristics of HCAs as well as their rare ability to undergo malignant transformation is useful in differentiating HCAs from focal nodular hyperplasia.

The Distal Spine: Normal Embryogenesis and Derangements Leading to Malformation.

The spine and spinal cord are composed of multiple segments initiated by different embryologic mechanisms and advanced under different systems of control. In humans, the upper central nervous system is formed by primary neurulation, the lower by secondary neurulation, and the intervening segment by junctional neurulation. This article focuses on the distal spine and spinal cord to address their embryogenesis and the molecular derangements that lead to some distal spinal malformations.

Retrieval of Inferior Vena Cava Filters Temporarily Placed in a Suprarenal Position: A Review of 13 Patients.

PURPOSE: To evaluate the safety and efficacy of retrieval of inferior vena cava filters (IVCF) temporarily placed in a suprarenal position. METHODS: Retrieval of IVCF placed in a suprarenal position was performed in 13 patients (5 men and 8 women; mean age: 45.1 ± 13.8 years) between July 2006 and May 2018 using either a loop snare technique or endobronchial forceps. Electronic medical records were reviewed for patient demographics and procedural information. RESULTS: Inferior vena cava filters retrieved included Option Elite (n = 9, 69%) and Günther Tulip (n = 4, 31%). Caval thrombosis was not detected in any patients on pre- or postretrieval cavogram. Eleven suprarenal IVCF (84%) were retrieved during the first retrieval attempt after a median indwelling time of 1.8 months (range, 0.03-12.10 months). Retrieval was initially unsuccessful in 2 (16%) patients with Option Elite filters, but both were successfully removed on second attempt using endobronchial forceps. Thirteen suprarenal IVCF (100%) were ultimately retrieved. CONCLUSION: Endovascular retrieval of IVCF temporarily placed in a suprarenal position is safe and efficacious.

Patient Experience and Preference in Transradial versus Transfemoral Access during Transarterial Radioembolization: A Randomized Single-Center Trial.

PURPOSE: To determine patient preference for transradial access (TRA) or transfemoral access (TFA) after experiencing both. MATERIALS AND METHODS: A randomized controlled crossover trial was conducted at a single institution. Thirty patients with hepatocellular carcinoma undergoing mapping and transarterial radioembolization (TARE) were enrolled to experience 1 TRA and 1 TFA procedure each, with randomization of which access approach was experienced first. Surveys assessing pain and quality of life (QOL) were administered after each procedure. Access site preference was collected after completion of both procedures. RESULTS: Twenty-two subjects (73.3%) preferred TRA, 4 (13.3%) preferred TFA, and 4 (13.3%) had no preference; 14 (46.7%) reported bruising after TRA, and 17 (53.3%) reported bruising after TFA. TRA was associated with significantly lower pain scores overall during the procedure, at the access site during the procedure, and in the recovery room compared with TFA (2.0 vs 2.9, P = .0046; 2.0 vs 3.0, P = .0004; 2.1 vs 2.9, P = .0357). Pain score after discharge was not significantly different (1.4 vs 1.5, P = .4235). QOL scores were not significantly different between TRA and TFA. No significant differences were found for fluoroscopy time, air kerma, dose-area product, or procedure time between TRA and TFA for either mapping (P = .1442, P = .5871, P = .6667, P = .6131) or radioembolization (P = .8574, P = .2344, P = .1119, P =.8474). For radioembolizations, TRA had significantly shorter recovery times compared with TFA (108 min vs 153 min, P = .0193). CONCLUSIONS: Patients exhibited a strong preference for TRA. With TRA, patients experienced less periprocedural pain and shorter recovery times without significant differences in radiation exposure or procedure length.