Impact of Vaccination and the Omicron Variant on COVID-19-related Chest CT Findings: A Multicenter Study.

Background The SARS-CoV-2 Omicron variant has a higher infection rate than previous variants but results in less severe disease. However, the effects of Omicron and vaccination on chest CT findings are difficult to evaluate. Purpose To investigate the effect of vaccination status and predominant variant on chest CT findings, diagnostic scores, and severity scores in a multicenter sample of consecutive patients referred to emergency departments for proven COVID-19. Materials and Methods This retrospective multicenter study included adults referred to 93 emergency departments with SARS-CoV-2 infection according to a reverse-transcriptase polymerase chain reaction test and known vaccination status between July 2021 and March 2022. Clinical data and structured chest CT reports, including semiquantitative diagnostic and severity scores following the French Society of Radiology-Thoracic Imaging Society guidelines, were extracted from a teleradiology database. Observations were divided into Delta-predominant, transition, and Omicron-predominant periods. Associations between scores and variant and vaccination status were investigated with χ2 tests and ordinal regressions. Multivariable analyses evaluated the influence of Omicron variant and vaccination status on the diagnostic and severity scores. Results Overall, 3876 patients were included (median age, 68 years [quartile 1 to quartile 3 range, 54-80]; 1695 women). Diagnostic and severity scores were associated with the predominant variant (Delta vs Omicron, χ2 = 112.4 and 33.7, respectively; both P < .001) and vaccination status (χ2 = 243.6 and 210.1; both P < .001) and their interaction (χ2 = 4.3 [P = .04] and 28.7 [P < .001], respectively). In multivariable analyses, Omicron variant was associated with lower odds of typical CT findings than was Delta variant (odds ratio [OR], 0.46; P < .001). Two and three vaccine doses were associated with lower odds of demonstrating typical CT findings (OR, 0.32 and 0.20, respectively; both P < .001) and of having high severity score (OR, 0.47 and 0.33, respectively; both P < .001), compared with unvaccinated patients. Conclusion Both the Omicron variant and vaccination were associated with less typical chest CT manifestations of COVID-19 and lesser extent of disease. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Yoon and Goo in this issue.

Cardiac MRI Features and Prognostic Value in Immune Checkpoint Inhibitor-induced Myocarditis.

Background Cardiac MRI features are not well-defined in immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M), a severe complication of ICI therapy in patients with cancer. Purpose To analyze the cardiac MRI features of ICI-M and to explore their prognostic value in major adverse cardiovascular events (MACE). Materials and Methods In this retrospective study from May 2017 to January 2020, cardiac MRI findings (including late gadolinium enhancement [LGE], T1 and T2 mapping, and extracellular volume fraction [ECV] z scores) of patients with ICI-M were compared with those of patients with cancer scheduled to receive ICI therapy (pre-ICI group) and patients with viral myocarditis. As a secondary objective, the potential value of cardiac MRI for predicting MACE in patients with ICI-M by using Cox proportional hazards models was explored. Results Thirty-three patients with ICI-M (mean age ± standard deviation, 68 years ± 14; 23 men) were compared with 21 patients scheduled to receive to ICI therapy (mean age, 65 years ± 14; 14 men) and 85 patients with viral myocarditis (mean age, 32 years ± 13; 67 men). Compared with the pre-ICI group, patients with ICI-M showed higher global native T1, ECV, and T2 z scores (0.03 ± 0.85 vs 1.79 ± 1.93 [P < .001]; 1.34 ± 0.57 vs 2.59 ± 1.97 [P = .03]; and -0.76 ± 1.41 vs 0.88 ± 1.96 [P = .002], respectively), and LGE was more frequently observed (27 of 33 patients [82%] vs two of 21 [10%]; P < .001). LGE was less frequent in patients with ICI-M than those with viral myocarditis (27 of 33 patients [82%] vs 85 of 85 [100%]; P < .001) but was more likely to involve the septal segments (16 of 33 patients [48%] vs 25 of 85 [29%]; P < .001) and midwall layer (11 of 33 patients [33%] vs two of 85 [2%]; P < .001). Septal LGE was the only cardiac MRI predictor of MACE at 1 year even after adjustment for peak troponin (adjusted hazard ratio, 2.7 [95% CI: 1.1, 6.7]; P = .03). Conclusion Cardiac MRI features of immune checkpoint inhibitor (ICI)-induced myocarditis (ICI-M) seem to differ from those in patients scheduled to receive ICIs and patients with viral myocarditis. Septal late gadolinium enhancement might be a predictor of major cardiovascular events in patients with ICI-M. Clinical trial registration no. NCT03313544 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Edelman and Pursnani in this issue.

Allosteric modulation of AMPA receptors counteracts Tau-related excitotoxic synaptic signaling and memory deficits in stress- and Aß-evoked hippocampal pathology.

Despite considerable progress in the understanding of its neuropathology, Alzheimer's disease (AD) remains a complex disorder with no effective treatment that counteracts the memory deficits and the underlying synaptic malfunction triggered by the accumulation of amyloid beta (Aß) and Tau protein. Mounting evidence supports a precipitating role for chronic environmental stress and glutamatergic excitotoxicity in AD, suggesting that targeting of glutamate receptor signaling may be a promising approach against both stress and AD pathologies. In light of the limited cognitive benefit of the direct antagonism of NMDA receptors in AD, we here focus on an alternative way to modify glutamatergic signaling through positive allosteric modulation of AMPA receptors, by the use of a PAM-AMPA compound. Using non-transgenic animal model of Aß oligomer injection as well as the combined stress and Aß i.c.v. infusion, we demonstrate that positive allosteric modulation of AMPA receptors by PAM-AMPA treatment reverted memory, but not mood, deficits. Furthermore, PAM-AMPA treatment reverted stress/Aß-driven synaptic missorting of Tau and associated Fyn/GluN2B-driven excitotoxic synaptic signaling accompanied by recovery of neurotransmitter levels in the hippocampus. Our findings suggest that positive allosteric modulation of AMPA receptors restores synaptic integrity and cognitive performance in stress- and Aß-evoked hippocampal pathology. As the prevalence of AD is increasing at an alarming rate, novel therapeutic targeting of glutamatergic signaling should be further explored against the early stages of AD synaptic malfunction with the goal of attenuating further synaptic damage before it becomes irreversible.

A study of the interplay effect for VMAT SBRT using a four-axes motion phantom.

PURPOSE: To assess the accuracy of volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) when treating moving targets (such as lung or liver lesions), focusing on the impact of the interplay effect in the event of complex breathing motion and when a gating window is used. METHODS: A dedicated programmable motion platform was implemented. This platform can carry large quality assurance (QA) phantoms and achieve complex three-dimensional (3D) motion. Volumetric modulated arc therapy SBRT plans were delivered with TrueBeam linac to this moving setup and the measured dose was compared to the computed one. Several parameters were assessed such as breathing period, dose rate, dose prescription, shape of the breathing pattern, the use of a planning target volume (PTV) margin, and the use of a gating window. RESULTS: Loss of dose coverage (D95%) was acceptable in most situations. The doses received by 95% of the CTV, D95% ( C T V m ) ranged from 94 to 101% (mean 98%) and the doses received by 2% of the CTV D2% ( C T V m ) ranged from 94% to 110% of the prescribed dose. A visible interplay effect was observed when no margin was used or when the number of breathing cycles during the treatment delivery was lower than 20. CONCLUSIONS: In our clinical context, treating lung and liver lesions using VMAT SBRT is reasonable. The interplay effect was moderated and acceptable in all simulated situations.

Parotid gland metastasis from prostate cancer: is docetaxel still the best treatment option?

Metastases of prostate cancer originating from the parotid gland are rare. However, this presentation raises the question of the management of visceral metastasis in castration-resistant prostate cancer. We report the case of an 87-year-old man who presented with a right painless parotid mass in the context of castration-resistant prostate cancer, indicating progression of the disease. He received medical treatment based on docetaxel. Here, we discuss the impact of new hormonotherapies such as enzalutamide and abiraterone acetate, which may be used for the management of these patients.

Peripherally inserted central catheter placement in cancer patients with profound thrombocytopaenia: a prospective analysis.

OBJECTIVE: No studies have specifically evaluated the safety of peripherally inserted central catheter (PICC) placement in patients with profound thrombocytopaenia. We prospectively determined the frequency of haemorrhagic complications of PICC placement in cancer patients with uncorrected profound thrombocytopaenia. METHODS: Profound thrombocytopaenia was defined as a platelet count <50 × 10(9)/l. No patients received transfusions before or after the procedure. Three types of adverse effects were analysed: minor oozing, mild haematoma and major haemorrhage. RESULTS: One hundred and forty-three PICC implantations in 101 cancer patients were prospectively included in the study: seven patients (7 %) had a solid tumour and 94 (93 %) a haematological malignancy. Among these 143 procedures in thrombocytopaenic patients, 93 (65 %) were performed with a platelet count 20-50 × 10(9)/l and 50 (35 %) had lower than 20 × 10(9)/l. No major haemorrhage was observed. Minor oozing was observed in six implantations (4 %) and mild haematoma in two (1.5 %), for a total of eight minor haemorrhagic adverse events (5.5 %). In patients with a platelet count <20 × 10(9)/l, 1/50 (2 %) had minor oozing and none had minor haematoma. CONCLUSIONS: In cancer patients with uncorrected profound thrombocytopaenia, the incidence of adverse events after PICC implantation was low, and was limited to minor haemorrhagic adverse events. KEY POINTS: • PICC placement has high technical success in profound thrombocytopaenic cancer patients. • Few adverse events are encountered after PICC placement, limited to minor haemorrhage. • PICC placement does not routinely require platelet transfusion in patients with thrombocytopaenia. • Such PICC placement still seems safe when the platelet count is <20 × 10 (9) /l.

Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided vertebroplasty.

PURPOSE: To prospectively evaluate the incidence of pulmonary cement embolism (PCE) after vertebroplasty in procedures performed under real-time computed tomographic (CT) fluoroscopy guidance. MATERIALS AND METHODS: A total of 85 vertebroplasties were performed in 51 consecutive patients (31 women, 20 men; mean age, 71.9 y; range, 48-92 y) in 51 sessions. The needle was inserted with guidance from intermittent single-shot CT scans, and intermittent CT fluoroscopy was used during cement injection only. To reduce the risk of extravertebral or extraosseous leakage, several procedures (cement injection stopping/slowing, needle position changes) were employed. The chest and treated bone were scanned immediately after vertebroplasty. These CT images included the entire thorax as well as the treated vertebrae. RESULTS: No cement emboli were observed on CT after vertebroplasty. After 85 vertebroplasty procedures, 44 extravertebral leaks were detected. Epidural leaks were observed on CT in six treated vertebrae (7%), in 12 cases in the anterior external venous plexus (14.1%), in five in the azygos vein (5.8%), in 19 in the disc space (22%), and in two in the foraminal space (2.3%). On a per-patient basis, the odds of leaks increased with the number of vertebroplasties (P = .05) and the volume of cement used (P = .0412). There was also a higher probability of leak (P < .05) for osteoporotic vertebral compression fractures (67.9%; 95% confidence interval, 47.7%-84.1%) than osteolytic spinal metastases (34.8%; 16.4%-57.3%). CONCLUSIONS: PCE did not occur after vertebroplasty under CT fluoroscopy guidance. Further larger prospective vertebroplasty studies are needed to compare the rates of PCE for CT versus conventional fluoroscopic guidance.

Specific DMPK-promoter targeting by CRISPRi reverses myotonic dystrophy type 1-associated defects in patient muscle cells.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3' untranslated region of the DMPK gene, thus leading to the expression of transcripts containing expanded CUG repeats (CUGexp). The pathophysiology is explained by a toxic RNA gain of function where CUGexp RNAs form nuclear aggregates that sequester and alter the function of MBNL splicing factors, triggering splicing misregulation linked to the DM1 symptoms. There is currently no cure for DM1, and most therapeutic strategies aim at eliminating CUGexp-DMPK transcripts. Here, we investigate a DMPK-promoter silencing strategy using CRISPR interference as a new alternative approach. Different sgRNAs targeting the DMPK promoter are evaluated in DM1 patient muscle cells. The most effective guides allowed us to reduce the level of DMPK transcripts and CUGexp-RNA aggregates up to 80%. The CUGexp-DMPK repression corrects the overall transcriptome, including spliceopathy, and reverses a physiological parameter in DM1 muscle cells. Its action is specific and restricted to the DMPK gene, as confirmed by genome-wide expression analysis. Altogether, our findings highlight DMPK-promoter silencing by CRISPRi as a promising therapeutic approach for DM1.

Chest computed tomography improvement in patients with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: Early report.

RATIONALE AND OBJECTIVES: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionised the treatment of cystic fibrosis (CF). Chest computed tomography (CT) is key in the diagnosis and follow-up of anatomical damage to the lungs. Our study aimed to evaluate changes on lung CT scans of patients with CF after receiving elexacaftor-tezacaftor-ivacaftor (ETI) therapy for one year. MATERIALS AND METHODS: We conducted a retrospective, observational, single-centre study between 2018 and 2021 on adult patients with CF administered ETI. We reviewed chest CT scans before and at least one year after starting ETI. The Brody-II score (BSII) was measured by two experienced radiologists who were blinded to the treatment. Paranasal sinus CT scans and clinical and functional data were also compared. Wilcoxon tests were used to compare differences, and Spearman's correlation coefficient was used to evaluate changes in forced expiratory volume in one second (FEV1) and total BSII. RESULTS: In the period, 63 patients were given ETI, and 12 met the criteria for analysis. The inter-observer reproducibility of BSII was satisfactory (intraclass correlation coefficient = 0.83, 95% confidence interval 0.57-0.91). The BSII decreased after one year of treatment (-18 ±â€¯16, p = 0.002) due to lower mucous plugging (-7 ±â€¯4, p < 0.001) and peribronchial thickening (-9 ±â€¯10, p = 0.002) scores. Bronchial, parenchymal, and hyperinflation scores were unchanged. Clinical and functional parameters were significantly improved, except for total lung capacity. The correlation between ΔFEV1 and Δtotal BSII was strong (r = 0.88, p < 0.001). The paranasal sinus CT score significantly improved with ETI treatment. CONCLUSIONS: ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment.

Brachytherapy for uterine cervix-limited acute myeloid leukemia relapse.

Acute myeloid leukemia (AML) may extend to extra-medullary sites at diagnosis or at relapse, either isolated or associated with bone marrow disease. Granulocytic sarcoma of uterine cervix is rare, and there is no established treatment for this disease. Two cases of uterine cervix-limited AML relapse showed that brachytherapy may be an effective therapeutic option in this setting along with chemotherapy, with good tolerance.

Computed Tomographic Changes in Patients with Cystic Fibrosis Treated by Combination Therapy with Lumacaftor and Ivacaftor.

BACKGROUND: As Cystic Fibrosis (CF) treatments drastically improved in recent years, tools to assess their efficiency need to be properly evaluated, especially cross-sectional imaging techniques. High-resolution computed tomography (HRCT) scan response to combined lumacaftor- ivacaftor therapy (Orkambi®) in patients with homozygous for F508del CFTR has not yet been assessed. METHODS: We conducted a retrospective observational study in two French reference centers in CF in Marseille hospitals, including teenagers (>12 years old) and adults (>18 years) who had received lumacaftor-ivacaftor and for whom we had at disposal at least two CT scans, one at before therapy and one at least six months after therapy start. CT scoring was performed by using the modified version of the Brody score. RESULTS: 34 patients have been included. The mean age was 26 years (12-56 years). There was a significant decrease in the total CT score (65.5 to 60.3, p = 0.049) and mucous plugging subscore (12.3 to 8.7, p = 0.009). Peribronchial wall thickening (PWT) was significantly improved only in the adult group (29.1 to 27.0, p = 0.04). Improvements in total score, peribronchial thickening, and mucous pluggings were significantly correlated with improvement in FEV1 (forced expiratory volume in 1 s). CONCLUSIONS: Treatment with lumacaftor-ivacaftor was associated with a significant improvement in the total CT score, which was mainly related to an improvement in mucous pluggings.

Transthoracic Doppler echocardiography during a military mission in a French role II in Mali: is it useful to learn this practice?

INTRODUCTION: Ultrasound is now recognized as a key tool in the practice of medicine in isolated situations. This study aims to evaluate the impact of transthoracic echocardiography (TTE) in a military mission when performed by a trained military practitioner (MP). MATERIALS AND METHODS: We conducted a 2-month retrospective observational study on the use of TTE in a French medical complex in Mali with a mission that included providing a medical aid to the population. All patients were included. Every ultrasound performed by the MP was listed, and the epidemiologic data, indication for the exam and results were collected for each TTE. RESULTS: A total of 349 patients were included, 16 were war-wounded patients and 333 came for a general medical consultation. In all, 153 ultrasounds were performed, including 48 TTEs. Sixteen TTEs were performed to evaluate injuries in war-wounded patients. During the 333 medical consultations, 32 TTEs were realized. The indications were dyspnoea (10), heart murmur (7), acute chest pain (5) and assessment of heart disease (10). TTE permitted a direct positive diagnosis for 18 patients: 7 with acute heart failure and 11 with morphologic problems. The normality of the exam was a supplementary argument to exclude a cardiac implication for eight patients. CONCLUSIONS: TTE can provide important information with a direct impact on the management of patients. Faced with cardiac emergencies, an adapted training can be proposed for the MP. Thereby, the transfer of conventional cardiac views could facilitate the advice of a cardiologist.

The GIRAFE phase II trial on MVCT-based "volumes of the day" and "dose of the day" addresses when and how to implement adaptive radiotherapy for locally advanced head and neck cancer.

During exclusive curative radiotherapy for head and neck tumors, the patient's organs at risk (OAR) and target volumes frequently change size and shape, leading to a risk of higher toxicity and lower control than expected on planned dosimetry. Adaptive radiotherapy is often necessary but 1) tools are needed to define the optimal time for replanning, and 2) the subsequent workflow is time-consuming. We designed a prospective study to evaluate 1) the validity of automatically deformed contours on the daily MVCT, in order to safely use the "dose-of the day" tool to check daily if replanning is necessary; 2) the automatically deformed contours on the replanning CT and the time gained in the replanning workflow. Forty-eight patients with T3-T4 and/or involved node >2 cm head and neck squamous cell carcinomas, planned for curative radiotherapy without surgery, will be enrolled. They will undergo treatment with helical IMRT including daily repositioning MVCTs. The contours proposed will be compared weekly on intermediate planning CTs (iCTs) on weeks 3, 4, 5 and 6. On these iCTs both manual recontouring and automated deformable registration of the initial contours will be compared with the contours automatically defined on the MVCT. The primary objective is to evaluate the Dice similarity coefficient (DSC) of the volumes of each parotid gland. The secondary objectives will evaluate, for target volumes and all OARs: the DSC, the mean distance to agreement, and the average surface-to-surface distance. Time between the automatic and the manual recontouring workflows will be compared.

Peripherally Inserted Central Catheter-Related Infections in a Cohort of Hospitalized Adult Patients.

PURPOSE: To determine the incidence and the risks factors of peripherally inserted central catheter (PICC)-related infectious complications. MATERIALS AND METHODS: Medical charts of every in-patient that underwent a PICC insertion in our hospital between January 2010 and October 2013 were reviewed. All PICC-related infections were recorded and categorized as catheter-related bloodstream infections (CR-BSI), exit-site infections, and septic thrombophlebitis. RESULTS: Nine hundred and twenty-three PICCs were placed in 644 unique patients, mostly male (68.3%) with a median age of 58 years. 31 (3.4%) PICC-related infections occurred during the study period corresponding to an infection rate of 1.64 per 1000 catheter-days. We observed 27 (87.1%) CR-BSI, corresponding to a rate of 1.43 per 1000 catheter-days, 3 (9.7%) septic thrombophlebitis, and 1 (3.2%) exit-site infection. Multivariate logistic regression analysis showed a higher PICC-related infection rate with chemotherapy (odds ratio (OR) 7.2-confidence interval (CI) 95% [1.77-29.5]), auto/allograft (OR 5.9-CI 95% [1.2-29.2]), and anti-coagulant therapy (OR 2.2-95% [1.4-12]). CONCLUSION: Chemotherapy, auto/allograft, and anti-coagulant therapy are associated with an increased risk of developing PICC-related infections. CLINICAL ADVANCE: Chemotherapy, auto/allograft, and anti-coagulant therapy are important predictors of PICC-associated infections. A careful assessment of these risk factors may be important for future success in preventing PICC-related infections.

Evaluation of PICC complications in orthopedic inpatients with bone infection for long-term intravenous antibiotics therapy.

PURPOSE: The purpose of this study is to evaluate the complications of peripherally inserted central catheters (PICCs) in orthopedic patients with chronic bone orthopedic infection. MATERIALS AND METHODS: The institutional review board approved this retrospective study and informed consent was waived. Records of 180 consecutives PICCs placed in patients hospitalized in the orthopedic surgery department were reviewed. All patients had bones infections necessitating a long-term intravenous antibiotics therapy. All PICC complications were recorded during the patient hospitalization: infection [catheter-related bloodstream infection (CRBSI), central line associated bloodstream infection (CLABSI), exit-site infection, septic phlebitis], thrombosis, occlusion, mechanical complication (accidental withdrawal, malposition, median nerve irritation). RESULTS: One hundred and eighty PICCs were placed in 136 patients. Mean duration of catheterization was 21 days (total 3911 PICC-days). Thirty-six PICCs (20%) were removed due to complications (9.2 complications per 1000 PICC-days): 14 (8%) infections (one CRBSI (Pseudomonas aeruginosa), one septic phlebitis (P. aeruginosa), two exit-site infections and 10 CLABSIs), 11 (6%) occlusions, and 12 (7%) mechanical complications (10 accidental withdrawals, one malposition, one median nerve irritation). One patient had two complications simultaneously. After multivariate analysis, two risk factors were significantly associated with the overall occurrence of complications: age more than 70 years [OR = 2.89 (1.06-7.89], p = 0.04] and number of lumen at least two [OR = 2.64 (1.03-6.75), p = 0.04]. CONCLUSIONS: Even in orthopedic patients with chronic orthopedic bone infection, PICCs have a low rate of complication. The increasing lumen number of the PICC is a potential risk factor in our series.

Apoptosis and p53 are not involved in the anti-tumor efficacy of ¹²5I-labeled monoclonal antibodies targeting the cell membrane.

INTRODUCTION: (125)I-labeled monoclonal antibodies ((125)I-mAbs) can efficiently treat small solid tumors. Here, we investigated the role of apoptosis, autophagy and mitotic catastrophe in (125)I-mAb toxicity in p53(-/-) and p53(+/+) cancer cells. METHODS: We exposed p53(-/-) and p53(+/+) HCT116 cells to increasing activities of internalizing (cytoplasmic location) anti-HER1 (125)I-mAbs, or non-internalizing (cell surface location) anti-CEA (125)I-mAbs. For each targeting model we established the relationship between survival and mean nucleus absorbed dose using the MIRD formalism. RESULTS: In both p53(-/-) and p53(+/+) HCT116 cells, anti-CEA (125)I-mAbs were more cytotoxic per Gy than anti-HER1 (125)I-mAbs. Sensitivity to anti-CEA (125)I-mAbs was p53-independent, while sensitivity to anti-HER1 (125)I-mAbs was higher in p53(-/-) HCT 116 cells, suggesting that they act through different signaling pathways. Apoptosis was only induced in p53(+/+) HCT116 cells and could not explain cell membrane radiation sensitivity. Inhibition of autophagy did not modify the cell response to (125)I-mAbs. By contrast, mitotic death was similarly induced in both p53(-/-) and p53(+/+) HCT116 cells by the two types of (125)I-mAbs. We also showed using medium transfer experiments that γ-H2AX foci were produced in bystander cells. CONCLUSION: Cell membrane sensitivity to (125)I-mAbs is not mediated by apoptosis and is p53-independent. Bystander effects-mediated mitotic death could be involved in the efficacy of (125)I-mAbs binding cell surface receptors.