Value of 18 F-FDG PET/CT to Identify Occult Infection in Presumed Aseptic Pseudarthrosis after Spinal Fusion: Correlation with Intraoperative Cultures.

Objective Fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) has gained attention as an emerging tool in case of suspicion of infection on spine, whether native or instrumented. However, the diagnostic performance of 18 F-FDG PET/CT in clinically occult low-grade surgical site infection (SSI) after spinal fusion, an important risk factor for pseudarthrosis, remains unknown. Methods We retrospectively identified all the presumed aseptic patients with pseudarthrosis confirmed by revision surgery who underwent preoperative 18 F-FDG PET/CT scans performed between April 2019 and November 2022. These patients were presumed aseptic because they did not have clinical signs or laboratory tests suggestive of SSI, preoperatively. The PET/CT images were analyzed in consensus by two nuclear medicine physicians blinded to the clinical, biological, and imaging information. Visual assessment of increased uptake around cage/intervertebral disk space (and/or hardware) higher than background recorded from the first normal adjacent vertebra was interpreted as positive. Image data were also quantitatively analyzed by the maximum standardized uptake value as an index of 18 F-FDG uptake, and the ratio between the uptake around cage/intervertebral disk space (and/or hardware) and background recorded from the first normal adjacent vertebra was calculated. The final diagnosis of infection was based on intraoperative cultures obtained during pseudarthrosis revision surgery. Results Thirty-six presumed aseptic patients with surgically confirmed pseudarthrosis after spinal fusion underwent preoperative 18 F-FDG PET/CT scans. Cultures of samples from revisions found that 20 patients (56%) were infected. The most frequent isolated bacterium was Cutibacterium acnes ( C. acnes ) in 15 patients (75%), followed by coagulase-negative staphylococci (CNS) in 7 patients (33%). Two patients had co-infections involving both C. acnes and CNS. Of the 36 PET/CT studied in this study, 12 scans were true-negative, 10 true-positive, 10 false-negative, and 4 false-positive. This resulted in sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 50%, 75%, 71%, 55%, and 61%, respectively. Conclusion In presumed aseptic pseudarthrosis after spinal fusion, 18 F-FDG PET/CT offers good specificity (75%) but low sensitivity (50%) to identify occult SSI. The high prevalence (56%) of SSI, mostly caused by C. acnes (75%), found in our presumed aseptic cohort of patients supports the utility of systematic intraoperative cultures in revision cases for pseudarthrosis.

Diagnostic and Therapeutic Issues in Glioma Using Imaging Data: The Challenge of Numerical Twinning.

Glial tumors represent the leading etiology of primary brain tumors. Their particularities lie in (i) their location in a highly functional organ that is difficult to access surgically, including for biopsy, and (ii) their rapid, anisotropic mode of extension, notably via the fiber bundles of the white matter, which further limits the possibilities of resection. The use of mathematical tools enables the development of numerical models representative of the oncotype, genotype, evolution, and therapeutic response of lesions. The significant development of digital technologies linked to high-resolution NMR exploration, coupled with the possibilities offered by AI, means that we can envisage the creation of digital twins of tumors and their host organs, thus reducing the use of physical sampling.

Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?

Cytotoxic lymphocytes (CLs), specifically cytotoxic T lymphocytes and natural killer cells, are indispensable guardians of the immune system and orchestrate the recognition and elimination of cancer cells. Upon encountering a cancer cell, CLs establish a specialized cellular junction, known as the immunological synapse that stands as a pivotal determinant for effective cell killing. Extensive research has focused on the presynaptic side of the immunological synapse and elucidated the multiple functions of the CL actin cytoskeleton in synapse formation, organization, regulatory signaling, and lytic activity. In contrast, the postsynaptic (cancer cell) counterpart has remained relatively unexplored. Nevertheless, both indirect and direct evidence has begun to illuminate the significant and profound consequences of cytoskeletal changes within cancer cells on the outcome of the lytic immunological synapse. Here, we explore the understudied role of the cancer cell actin cytoskeleton in modulating the immune response within the immunological synapse. We shed light on the intricate interplay between actin dynamics and the evasion mechanisms employed by cancer cells, thus providing potential routes for future research and envisioning therapeutic interventions targeting the postsynaptic side of the immunological synapse in the realm of cancer immunotherapy. This review article highlights the importance of actin dynamics within the immunological synapse between cytotoxic lymphocytes and cancer cells focusing on the less-explored postsynaptic side of the synapse. It presents emerging evidence that actin dynamics in cancer cells can critically influence the outcome of cytotoxic lymphocyte interactions with cancer cells.

Machine learning decision tree models for multiclass classification of common malignant brain tumors using perfusion and spectroscopy MRI data.

Background: To investigate the contribution of machine learning decision tree models applied to perfusion and spectroscopy MRI for multiclass classification of lymphomas, glioblastomas, and metastases, and then to bring out the underlying key pathophysiological processes involved in the hierarchization of the decision-making algorithms of the models. Methods: From 2013 to 2020, 180 consecutive patients with histopathologically proved lymphomas (n = 77), glioblastomas (n = 45), and metastases (n = 58) were included in machine learning analysis after undergoing MRI. The perfusion parameters (rCBVmax, PSRmax) and spectroscopic concentration ratios (lac/Cr, Cho/NAA, Cho/Cr, and lip/Cr) were applied to construct Classification and Regression Tree (CART) models for multiclass classification of these brain tumors. A 5-fold random cross validation was performed on the dataset. Results: The decision tree model thus constructed successfully classified all 3 tumor types with a performance (AUC) of 0.98 for PCNSLs, 0.98 for GBM and 1.00 for METs. The model accuracy was 0.96 with a RSquare of 0.887. Five rules of classifier combinations were extracted with a predicted probability from 0.907 to 0.989 for that end nodes of the decision tree for tumor multiclass classification. In hierarchical order of importance, the root node (Cho/NAA) in the decision tree algorithm was primarily based on the proliferative, infiltrative, and neuronal destructive characteristics of the tumor, the internal node (PSRmax), on tumor tissue capillary permeability characteristics, and the end node (Lac/Cr or Cho/Cr), on tumor energy glycolytic (Warburg effect), or on membrane lipid tumor metabolism. Conclusion: Our study shows potential implementation of machine learning decision tree model algorithms based on a hierarchical, convenient, and personalized use of perfusion and spectroscopy MRI data for multiclass classification of these brain tumors.

Correlative light and electron microscopy to explore the lytic immunological synapse between natural killer cells and cancer cells.

Cytotoxic lymphocytes, such as natural killer (NK) cells and cytotoxic T cells, can recognize and kill tumor cells by establishing a highly specialized cell-cell contact called the immunological synapse. The formation and lytic activity of the immunological synapse are accompanied by local changes in the organization, dynamics and molecular composition of the cell membrane, as well as the polarization of various cellular components, such as the cytoskeleton, vesicles and organelles. Characterization and understanding of the molecular and cellular processes underlying immunological synapse formation and activity requires the combination of complementary types of information provided by different imaging modalities, the correlation of which can be difficult. Correlative light and electron microscopy (CLEM) allows for the accurate correlation of functional information provided by fluorescent light microscopy with ultrastructural features provided by high-resolution electron microscopy. In this chapter, we present a detailed protocol describing each step to generate cell-cell conjugates between NK cells and cancer cells, and to analyze these conjugates by CLEM using separate confocal laser-scanning and transmission electron microscopes.

Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus.

The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells. We found that F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13. Our data suggest that CRP2 and SRF cooperate to modulate of MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant metastasis-free survival in breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in breast cancer cells.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Artificial Intelligence for Automated DWI/FLAIR Mismatch Assessment on Magnetic Resonance Imaging in Stroke: A Systematic Review.

We conducted this Systematic Review to create an overview of the currently existing Artificial Intelligence (AI) methods for Magnetic Resonance Diffusion-Weighted Imaging (DWI)/Fluid-Attenuated Inversion Recovery (FLAIR)-mismatch assessment and to determine how well DWI/FLAIR mismatch algorithms perform compared to domain experts. We searched PubMed Medline, Ovid Embase, Scopus, Web of Science, Cochrane, and IEEE Xplore literature databases for relevant studies published between 1 January 2017 and 20 November 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the included studies using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Five studies fit the scope of this review. The area under the curve ranged from 0.74 to 0.90. The sensitivity and specificity ranged from 0.70 to 0.85 and 0.74 to 0.84, respectively. Negative predictive value, positive predictive value, and accuracy ranged from 0.55 to 0.82, 0.74 to 0.91, and 0.73 to 0.83, respectively. In a binary classification of ±4.5 h from stroke onset, the surveyed AI methods performed equivalent to or even better than domain experts. However, using the relation between time since stroke onset (TSS) and increasing visibility of FLAIR hyperintensity lesions is not recommended for the determination of TSS within the first 4.5 h. An AI algorithm on DWI/FLAIR mismatch assessment focused on treatment eligibility, outcome prediction, and consideration of patient-specific data could potentially increase the proportion of stroke patients with unknown onset who could be treated with thrombolysis.

An integrated workflow for phosphopeptide identification in natural killer cells (NK-92MI) and their targets (MDA-MB-231) during immunological synapse formation.

Here, we present a protocol to identify and quantify phosphopeptides during the dynamic formation of an immunological synapse. We describe steps for mixing isotope-labeled immune and target cells, the stabilization of cell-to-cell conjugates by cross-linking, and their isolation by fluorescence-activated cell sorting. We detail the isolation of phosphopeptides by phosphopeptide enrichment and their subsequent measurement by mass spectrometry. Finally, we describe the analysis of the resulting data to separate cell-specific phosphopeptides using the isotope label and label-free quantification.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

18 F-NaF PET/CT in Presumed Aseptic Pseudarthrosis after Spinal Fusion: Correlation with Findings at Revision Surgery and Intraoperative Cultures.

Background Conventional imaging is useful to assess interbody fusion by showing complete trabecular bony bridging, but has a low positive predictive value for pseudarthrosis. Because alterations of bone metabolism may precede structural anatomical changes on computed tomography (CT), we aimed to investigate the ability of fluorine 18 sodium fluoride positron emission tomography/computed tomography ( 18 F-NaF PET/CT) to identify pseudarthrosis after spinal fusion using surgical revision as the reference standard. Methods We retrospectively reviewed 18 F-NaF PET/CT scans performed between February 2019 and September 2020 in patients experiencing pain after spinal fusion. We included the 18 patients who underwent revision surgery for suspicion of pseudarthrosis. Five consecutive patients who were clearly fused on CT served as the control group. Results In the revision surgery group ( n =18), visual assessment by 18 F-NaF PET/CT revealed that all 22 cages with an increased 18 F-NaF uptake around intercorporal fusion material had mobility at revision surgery, whereas none of the fused patients ( n =5) showed uptake around cage/intervertebral disk space. Among the 18 patients with presumed aseptic pseudarthrosis, intraoperative cultures revealed surgical site infection (SSI) caused by Cutibacterium acnes ( C. acnes ) in seven patients (38.9%). There was a statistically significant difference in standardized uptake values and uptake ratios between the revision surgery and control groups ( p =5.3× 10 -6 and p =0.0002, respectively). Conclusions 18 F-NaF PET/CT imaging appeared as a useful tool to identify pseudarthrosis following spinal fusion. The unexpectedly high prevalence (38.9%) of SSI caused by C. acnes found in presumed aseptic patients supports the utility of intraoperative cultures in revision cases for pseudarthrosis, even without preoperative clinical suspicion of SSI.

Automated Identification of Multiple Findings on Brain MRI for Improving Scan Acquisition and Interpretation Workflows: A Systematic Review.

We conducted a systematic review of the current status of machine learning (ML) algorithms' ability to identify multiple brain diseases, and we evaluated their applicability for improving existing scan acquisition and interpretation workflows. PubMed Medline, Ovid Embase, Scopus, Web of Science, and IEEE Xplore literature databases were searched for relevant studies published between January 2017 and February 2022. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The applicability of ML algorithms for successful workflow improvement was qualitatively assessed based on the satisfaction of three clinical requirements. A total of 19 studies were included for qualitative synthesis. The included studies performed classification tasks (n = 12) and segmentation tasks (n = 7). For classification algorithms, the area under the receiver operating characteristic curve (AUC) ranged from 0.765 to 0.997, while accuracy, sensitivity, and specificity ranged from 80% to 100%, 72% to 100%, and 65% to 100%, respectively. For segmentation algorithms, the Dice coefficient ranged from 0.300 to 0.912. No studies satisfied all clinical requirements for successful workflow improvements due to key limitations pertaining to the study's design, study data, reference standards, and performance reporting. Standardized reporting guidelines tailored for ML in radiology, prospective study designs, and multi-site testing could help alleviate this.

Causes and Risk Factors of Pediatric Spontaneous Intracranial Hemorrhage-A Systematic Review.

Previous studies suggest that the most common cause of spontaneous intracerebral hemorrhage in children and adolescents is arteriovenous malformations (AVMs). However, an update containing recently published data on pediatric spontaneous intracranial hemorrhages is lacking. The aim of this study is to systematically analyze the published data on the etiologies and risk factors of pediatric spontaneous intracranial hemorrhage. This systematic review was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search in PubMed, Embase, Scopus, Web of Science and Cochrane Library was conducted aiming for articles published in year 2000 and later, containing data on etiology and risk factors of spontaneous intracranial hemorrhages in unselected cohorts of patients aged between 1 month and 18 years. As a result, forty studies were eligible for data extraction and final analysis. These included 7931 children and adolescents with 4009 reported etiologies and risk factors. A marked variety of reported etiologies and risk factors among studies was observed. Vascular etiologies were the most frequently reported cause of pediatric spontaneous intracranial hemorrhages (n = 1727, 43.08% of all identified etiologies or risk factors), with AVMs being the most common vascular cause (n = 1226, 70.99% of all vascular causes). Hematological and systemic causes, brain tumors, intracranial infections and cardiac causes were less commonly encountered risk factors and etiologies.

How natural killer cells avoid self-destruction when killing their targets.

How cytotoxic lymphocytes are protected against their own weapons during close combat with diseased target cells is an important and long-standing question in immunology. A study in this issue provides new insights into the mechanisms by which natural killer (NK) cells avoid self-destruction.

Intrinsic Resistance of Chronic Lymphocytic Leukemia Cells to NK Cell-Mediated Lysis Can Be Overcome In Vitro by Pharmacological Inhibition of Cdc42-Induced Actin Cytoskeleton Remodeling.

Natural killer (NK) cells are innate effector lymphocytes with strong antitumor effects against hematologic malignancies such as chronic lymphocytic leukemia (CLL). However, NK cells fail to control CLL progression on the long term. For effective lysis of their targets, NK cells use a specific cell-cell interface, known as the immunological synapse (IS), whose assembly and effector function critically rely on dynamic cytoskeletal changes in NK cells. Here we explored the role of CLL cell actin cytoskeleton during NK cell attack. We found that CLL cells can undergo fast actin cytoskeleton remodeling which is characterized by a NK cell contact-induced accumulation of actin filaments at the IS. Such polarization of the actin cytoskeleton was strongly associated with resistance against NK cell-mediated cytotoxicity and reduced amounts of the cell-death inducing molecule granzyme B in target CLL cells. Selective pharmacological targeting of the key actin regulator Cdc42 abrogated the capacity of CLL cells to reorganize their actin cytoskeleton during NK cell attack, increased levels of transferred granzyme B and restored CLL cell susceptibility to NK cell cytotoxicity. This resistance mechanism was confirmed in primary CLL cells from patients. In addition, pharmacological inhibition of actin dynamics in combination with blocking antibodies increased conjugation frequency and improved CLL cell elimination by NK cells. Together our results highlight the critical role of CLL cell actin cytoskeleton in driving resistance against NK cell cytotoxicity and provide new potential therapeutic point of intervention to target CLL immune escape.

The multiple roles of actin-binding proteins at invadopodia.

Invadopodia are actin-rich membrane protrusions that facilitate cancer cell dissemination by focusing on proteolytic activity and clearing paths for migration through physical barriers, such as basement membranes, dense extracellular matrices, and endothelial cell junctions. Invadopodium formation and activity require spatially and temporally regulated changes in actin filament organization and dynamics. About three decades of research have led to a remarkable understanding of how these changes are orchestrated by sequential recruitment and coordinated activity of different sets of actin-binding proteins. In this chapter, we provide an update on the roles of the actin cytoskeleton during the main stages of invadopodium development with a particular focus on actin polymerization machineries and production of pushing forces driving extracellular matrix remodeling.

Efficacy of chest CT scan for COVID-19 diagnosis in a low prevalence and incidence region.

OBJECTIVES: Value of chest CT was mainly studied in area of high COVID-19 incidence. The aim of this study was therefore to evaluate chest CT performances to diagnose COVID-19 pneumonia with regard to RT-PCR as reference standard in a low incidence area. METHODS: A survey was sent to radiology department in 4 hospitals in an administrative French region of weak disease prevalence (3.4%). Study design was approved by the local institutional review board and recorded on the clinicaltrial.gov website (NCT04339686). Written informed consent was waived due to retrospective anonymized data collection. Patients who underwent a RT-PCR and a chest CT scan within 48 h for COVID-19 pneumonia suspicion were consecutively included. Diagnostic accuracy including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of chest CT regarding RT-PCR as reference standard were calculated. RESULTS: One hundred twenty-nine patients had abnormal chest CT findings compatible with a COVID-19 pneumonia (26%, 129/487). Among the 358 negative chest CT findings, 3% (10/358) were RT-PCR positive. Chest CT sensitivity, specificity, positive, and negative predictive value were respectively 87% (IC95: 85, 89; 69/79), 85% (IC95: 83, 87; 348/408), 53% (IC95: 50, 56; 69/129), and 97% (IC95: 95, 99; 348/358). CONCLUSIONS: In a low prevalence area, chest CT scan is a good diagnostic tool to rule out COVID-19 infection among symptomatic suspected patients. KEY POINTS: • In a low prevalence area (3.4% in the administrative area and 5.8% at mean in the study) chest CT sensitivity and specificity for diagnosing COVID-19 pneumonia were 87% and 85% respectively. • In patients with negative chest CT for COVID-19 pneumonia, the negative predictive value of COVID-19 infection was 97% (348/358 subjects). • Performance of CT was equivalent between the 4 centers participating to this study.

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France.

Background The role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student t test, χ2 test, and Pearson correlation coefficient. P < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful. © RSNA, 2021 Online supplemental material is available for this article.

Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.

Congenital defects of the immune system called primary immunodeficiency disorders (PID) describe a group of diseases characterized by a decrease, an absence, or a malfunction of at least one part of the immune system. As a result, PID patients are more prone to develop life-threatening complications, including cancer. PID currently include over 400 different disorders, however, the variety of PID-related cancers is narrow. We discuss here reasons for this clinical phenotype. Namely, PID can lead to cell intrinsic failure to control cell transformation, failure to activate tumor surveillance by cytotoxic cells or both. As the most frequent tumors seen among PID patients stem from faulty lymphocyte development leading to leukemia and lymphoma, we focus on the extensive genomic alterations needed to create the vast diversity of B and T lymphocytes with potential to recognize any pathogen and why defects in these processes lead to malignancies in the immunodeficient environment of PID patients. In the second part of the review, we discuss PID affecting tumor surveillance and especially membrane trafficking defects caused by altered exocytosis and regulation of the actin cytoskeleton. As an impairment of these membrane trafficking pathways often results in dysfunctional effector immune cells, tumor cell immune evasion is elevated in PID. By considering new anti-cancer treatment concepts, such as transfer of genetically engineered immune cells, restoration of anti-tumor immunity in PID patients could be an approach to complement standard therapies.