3C 220.3: a radio galaxy lensing a submillimeter galaxy

Herschel Space Observatory photometry and extensive multiwavelength followup have revealed that the powerful radio galaxy 3C 220.3 at z=0.685 acts as a gravitational lens for a background submillimeter galaxy (SMG) at z=2.221. At an observed wavelength of 1mm, the SMG is lensed into three distinct images. In the observed near infrared, these images are connected by an arc of 1.8" radius forming an Einstein half-ring centered near the radio galaxy. In visible light, only the arc is apparent. 3C 220.3 is the only known instance of strong galaxy-scale lensing by a powerful radio galaxy not located in a galaxy cluster and therefore it offers the potential to probe the dark matter content of the radio galaxy host. Lens modeling rejects a single lens, but two lenses centered on the radio galaxy host A and a companion B, separated by 1.5", provide a fit consistent with all data and reveal faint candidates for the predicted fourth and fifth images. The model does not require an extended common dark matter halo, consistent with the absence of extended bright X-ray emission on our Chandra image. The projected dark matter fractions within the Einstein radii of A (1.02") and B (0.61") are about 0.4 +/- 0.3 and 0.55 +/- 0.3. The mass to i-band light ratios of A and B, M/L ~ 8 +/- 4 Msun/Lsun, appear comparable to those of radio-quiet lensing galaxies at the same redshift in the CASTLES, LSD, and SL2S samples. The lensed SMG is extremely bright with observed f(250um) = 440mJy owing to a magnification factor mu~10. The SMG spectrum shows luminous, narrow CIV 154.9nm emission, revealing that the SMG houses a hidden quasar in addition to a violent starburst. Multicolor image reconstruction of the SMG indicates a bipolar morphology of the emitted ultraviolet (UV) light suggestive of cones through which UV light escapes a dust-enshrouded nucleus.Comment: 17 pages, 14 Figures, accepted for publication in Ap

Total 18F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

Positron emission tomography (PET) using 6-[(18)F]fluoro-L-dihydroxyphenylalanine ((18)F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. (18)F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total (18)F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an (18)F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on (18)F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. (18)F-dopa PET detected 979 lesions. SUV(max) on (18)F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with (18)F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

In-111-octreotide is superior to I-123-metaiodobenzylguanidine for scintigraphic detection of head and neck paragangliomas

In this study, we evaluated the diagnostic yield of somatostatin receptor scintigraphy (SRS), 1-metaiodobenzylguanidine (MIBG) scintigraphy, and morphologic imaging (CT or MRI) in patients with head and neck paragangliomas. Methods: In a university hospital setting, patients considered to have head and neck paraganglioma were referred to the outpatient endocrinology department and underwent CT or MRI, SRS, and MIBG imaging. For validation, we used a composite reference standard consisting of clinical and histologic data and CT or MRI, with which SRS and MIBG imaging were compared. Urinary metanelphrine and normetanephrine measurements were also obtained. Results: Twenty-nine consecutively referred patients (17 women and 12 men) were included and were found to have paraganglioma. Both morphologic and SRS were positive in 27 patients (sensitivity, 93%, and 95% confidence interval[CI], 77%-98%, compared with the composite reference standard), whereas MIBG was positive in only 13 patients (44%; 95% CI, 23%-61%) (P <0.001, compared with SRS). On a lesion-based analysis, morphologlic imaging detected 31 lesions (sensitivity, 82%; 95% CI, 65%92%), SRS detected 34 (89%; 95% CI, 75%-97%), and MIBG detected 15 (42%; 95% CI, 26%-59%). SRS was superior to MIBG (P = 0.001). With SRS, a previously unknown carcinoid tumor was detected in 1 patient, and a carcinoid was suspected in another patient. MIBG detected an additional adrenal pheochromocytoma in 1 patient. Urinary metanephrine or normetanephrine excretion was elevated in 6 patients. The number of lesions on SRS and MIBG per patient correlated with the levels of abnormal metanephrine or normetanelphrine excretion (P = 0.005 and P = 0.02, respectively). Conclusion: SRS was superior to MIBG in patients with highly suspected head and neck paraganglioma

Molecular imaging in neuroendocrine tumors:Molecular uptake mechanisms and clinical results

Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-systematic review is presented on receptor based and metabolic imaging methods. Receptor-based imaging covers the molecular backgrounds of somatostatin, vaso-intestinal peptide (VIP), bombesin and cholecystokinin (CCK) receptors and their link with nuclear imaging. Imaging methods based on specific metabolic properties include meta-iodo-benzylguanide (MIBG) and dimercapto-sulphuric acid (DMSA-V) scintigraphy as well as more modem positron emission tomography (PET)-based methods using radio-labeled analogues of amino acids, glucose, dihydroxyphenylalanine (DOPA), dopamine and tryptophan. Diagnostic sensitivities are presented for each imaging method and for each neuroendocrine tumor subtype. Finally, a Forest plot analysis of diagnostic performance is presented for each tumor type in order to provide a comprehensive overview for clinical use. (c) 2009 Elsevier Ireland Ltd. All rights reserved

(18)F-Dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: Relation to tumor differentiation

Curative treatment for recurrent medullary thyroid cancer (MTC), diagnosed by rising serum calcitonin, is surgery, but tumor localization is difficult. Therefore, the value of (18)F-dihy-droxyphenylanaline PET ((18)F-DOPA PET), (18)F-FDG PET, (99m)Tc-V-di-mercaptosulfuricacid (DMSA-V) scintigraphy, and MRI or CT was studied. Methods: Twenty-one patients with biochemical recurrent or residual MTC underwent (18)F-DOPA PET, (18)F-FDG PET, DMSA-V scintigraphy, and MRI or CT. Patient- and lesion-based sensitivities were calculated using a composite reference consisting of all imaging modalities. Results: In 76% of all patients with MTC, one or more imaging modalities was positive for MTC lesions. In 6 of 8 patients with a calcitonin level of <500 ng/L, imaging results were negative. In 15 patients with positive imaging results, (18)F-DOPA PET detected 13 (sensitivity, 62%; with 4.6 lesions per patient [Ipp]). Morphologic imaging (n = 19) was positive in 7 (sensitivity, 37%; 4.7 Ipp), DMSA-V (n - 18) in 5 (sensitivity, 28%; 1.1 Ipp), and (18)F-FDG PET (n = 17) in 4 (sensitivity, 24%; 1.6 Ipp). In a lesion-based analysis, (18)F-DOPA PET detected 95 of 134 lesions (sensitivity, 71 %), morphologic imaging detected 80 of 126 (sensitivity, 64%), DMSA-V detected 20 of 108 (sensitivity, 19%), and (18)F-FDG PET detected 48 of 102 (sensitivity, 30%). in 2 of 3 patients with a calcitonin/carcinoembryonic antigen (CEA) doubling time of 500 ng/L. (18)F-DOPA PET is superior to (18)F-FDG PET, DMSA-V, and morphologic imaging. With short calcitonin doubling times