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Background/Aims Adult-onset Still's disease is a systemic inflammatory disease of unknown aetiology. Post-COVID-19 vaccine adult-onset Still's disease has been reported and was associated with only mild myocarditis. Here we report the first case of adult-onset Still's disease after mRNA COVID-19 vaccination presenting with severe myocarditis with acute heart failure and cardiogenic shock. Methods We described the case history of the patient. Results A 72-year-old Chinese woman developed gradual onset of fever, shortness of breath, sore throat, generalised arthralgia, malaise and poor appetite 15 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. Physical examination revealed fever, bilateral ankle oedema and elevated jugular venous pressure. Significant investigation results are shown in Table 1. Extensive viral panel tests (including enterovirus, influenza and cytomegalovirus) were all negative. Echocardiography showed severely reduced left ventricular ejection fraction of 20%. The acute heart failure was complicated by cardiogenic shock requiring intensive care unit admission. Myocarditis was later diagnosed. Although the heart condition subsequently improved, there were persistent fever and arthralgia, as well as the development of generalised maculopapular skin rash. In view of that, series of investigations were performed, which revealed persistent neutrophilic leucocytosis, hyper-ferritinaemia and liver function derangement, while autoimmune panel was grossly unremarkable and septic/viral workup was negative (Table 1). Contrast PET-CT scan showed no features of malignancy. Adult-onset Still's disease was diagnosed, and the patient was treated with oral prednisolone 40mg daily. The patient's condition responded to the treatment;the fever subsided and the leucocyte count and inflammatory markers were normalised, and she was subsequently discharged. Three months after discharge, the patient was clinically well with prednisolone tapered down to 5mg daily. Reassessment echocardiogram showed full recovery with LVEF 60%. Conclusion Severe myocarditis with acute heart failure and cardiogenic shock is a possible initial presentation of adult-onset Still's disease after mRNA COVID-19 vaccination. After exclusion of more common aetiologies, it is important to consider adult-onset Still's disease as one of the differential diagnoses in the presence of compatible features following COVID-19 vaccination, such that appropriate and timely workup and treatment can be offered. (Table Presented).
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Objectives: COVID-19 posed profound challenges to nuclear medicine (NM) practice and education on an international scope. Initial lessons learned may be useful in understanding and optimizing dissemination of critical information during global disasters. To better understand the pandemic's initial manifold impact and responses that were in turn enacted, we systematically reviewed relevant articles published during the 2020 calendar year. Method(s): A librarian experienced in systematic reviews performed a rapid scoping review of the English language literature indexed in PubMed, Embase and Web of Science by crossing NM and COVID terms;445 citations were returned. Duplicate, extraneous, non-English and non-full text articles were excluded leaving 248 articles which were analyzed by origin, topic, design, and imaging details. Result(s): An array of topics, techniques, journals and countries of origin were encountered. 158 articles appeared in primary NMjournals, 26 appeared in generic radiology journals and 65 in non-imaging journals. Most frequent countries represented were USA (55), Italy (33), France (19) and UK (17), reflecting the hard-hit countries early during the pandemic. 118 clinical articles were case reports or small series of which 80 featured FDG-PET/CT. There were 36 observational studies. Among non-clinical topics, articles focused on safetymeasures (102), economics and recovery (23), remote reading (17) and education (8). There were 17 surveys. Society-based guidelines (47) and individual-group best practices (79) were published relating to cardiology (33), lung scintigraphy (12), andmultiple topics (48). Systematic (10) and narrative reviews (61) were less frequent than opinion articles (75). Frequent modalities discussed were FDG PET (156), nuclear cardiology (56) and lung scintigraphy (35). Conclusion(s): The medical literature has memorialized a robust response of information sharing during the initial challenges the COVID-19 pandemic relating to patient care, operations and education. Through scoping review, we have analyzed the nature of information disseminated. Opinions and single group best practices dominated the literature. Clinical reports during the first year were primarily case reports or small series, frequently FDG-PET/ CT. The nature of the literature matured as the year progressed, and sources of information broadened as the epidemic spread.
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Ziel/Aim The global SARS-CoV-2 vaccination campaign brought attention to a recent pitfall in tumor staging by PET/CT. Several publications reported a non-specific F-18-FDG tracer uptake in axillary lymph nodes after COVID-19 vaccination. Ga-68-FAPI PET/CT is a new oncologic imaging tool that may overcome this limitation. Methodik/Methods For this purpose, we compared the tracer uptake in a head-to-head and same-day F-18-FDG and Ga-68-FAPI PET/CT study. 11 patients from our prospective database (NCT04571086) were included showing vaccine-related tracer uptake in axillary lymph nodes up to 6 weeks after COVID- 19 vaccination. Ergebnisse/Results Among the total of 11 patients, all (n = 11) showed visual positive uptake in the lymph nodes ipsilateral to the injection side on F-18-FDG PET. None (n = 0) of the included patients showed significant tracer uptake on Ga-68-FAPI PET. Follow-up imaging confirmed reactive nodal uptake in all patients. The tumor detection efficacy for these patients was 73 % for F-18-FDG and 94 % for Ga-68-FAPI. Schlussfolgerungen/Conclusions In our case series, Ga-68-FAPI demonstrated resistance to vaccine-related pitfalls while presenting superior tumor detection.
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Ziel/Aim We aimed at evaluating the incidence of SARS-CoV2 vaccine-related axillary and supraclavicular hypermetabolic lymphadenopathy (HLA) and evaluate which timepoint produces the least number of false-positive findings in HLA. Methodik/Methods For this retrospective, multi-center imaging study patients with any form of SARS-CoV2 vaccination prior to 18F-FDG-PET/CT between January 2021 and December 2021 were included. Patients were divided into six groups according to the timepoint of vaccination prior to 18F-FDG-PET/CT imaging: Group 1 (0-6 Days), Group 2 (7-13 Days), Group 3 (14-20 Days), Group 4 (21-27 Days), Group 5 (28-34 Days) and Group 6 (35-80 Days). As reference SUVmax of mediastinal blood pool (MBP) and SUVmax contralateral reference lymph node (RL) were determined. For each group, the following parameters were assessed. A) absolute SUVmax of HLA B) incidence of HLA [defined as the ratio of SUVmaxHLA/ SUVmax Mediastinal Blood Pool (rHLA/MBP)] greater than 1,5 C) rHLA/MBP D) ratio SUVmax HLA vs. SUVmax contralateral reference lymph node (rHLA/RL). Ergebnisse/Results HLA showed the highest incidence in Group 1(day 0-6) 16/23 (70 %). Similarly, SUVmax HLA and rHLA/MBP were highest in this group, SUVmax 4.97 +/- 4.1 and 2.58 +/- 2.1 respectively. The incidence of HLA, SUVmax HLA, and rHLA/MBP were higher in Group 3 (14-20 days) than in Group 2 (7- 13days);57 % vs 44 %;5.05 +/- 4.33vs 3.9 +/- 2.81 (p = 0.723 and 2.32 +/- 1.8 vs 1.83 +/- 1.38(p = 0.788). All parameters for HLA dropped markedly after at least 21 days of vaccination. There were no significant differences in SUVmax HLA, rHLA/MBP and rHLA/RL in group 4 (21-27 days), group 5 (28-34 days) and group 6 (35-80 Days). [1] Schlussfolgerungen/Conclusions It is crucial for diagnostic physicians to assess the recent history of COVID-19 vaccination prior to FDG-PET/CT scan to reduce the risk of false-positive calls. If feasible, FDG PET should be postponed by at least 3 weeks after SARS-CoV2 vaccination especially if an accurate evaluation of axillary status is required.
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Objectives: In the Covid-19 era, there was a surge in the cases of a life-threatening infection of rhinosinonasal mucormycosis. Mucormycosis, popularly known as black fungus, is an infection caused by mycetes mucorales, an aseptate hyphae. Presently, computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used imaging modalities for the management of patients with rhinosinonasal mucormycosis. The present study was aimed to evaluate the role of 18F- FDG PET/CT in the detection of recurrent or residual disease in post-surgical or post antifungal therapy in these patients for further management. Method(s): A total of 10 patients were included in this pilot study of Covid-19 positive patients and histologically proven mucormycosis (by KOH mount). 18F- FDG PET/CT was performed to assess the disease status in 6 postoperative/ post debridement patients and response to antifungal therapy in 4 patients, at an interval of 40 (range = 27-66) days post intervention. Result(s): The mean age of the patients was 45.0 +/- 11.65 years. The male: female ratio was 9:1. The common clinical presentation was ipsilateral facial or orbital pain and swelling. Covid-19 infection was positive in all the patients except one who had CT finding with HRCT score of 10/25 and hence was considered as post Covid-19 infection. Six out of 10 patients were diabetic on oral hypoglycaemic agents or insulin. All patients had a baseline CT/MRI for staging the initial extent of the disease. Surgical debridement was done in 6 out of the 10 patients followed by antifungal therapy (Liposomal Amphotericin B and Pozaconazole). Remaining four patients were treated with antifungal therapy. PET/CTwas performed after an average of 40 days of surgical/medical intervention, in whom clinical symptoms persisted or worsened even on antifungal therapy. 18F-FDG PET/CT showed metabolically active residual disease in all the patients with a mean SUVmax of 9.78 +/- 4.03. Conclusion(s): In the era of ongoing Covid-19 infection, black fungus has been a debilitating disease with high mortality and morbidity. Present study demonstrated that 18F-FDG PET/CT can be an efficient imaging tool for an early surgical/ medical treatment response assessment and restaging.
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The [18F]FDG PET/CT is a crucial tool in the diagnostic process and monitoring of neoplastic diseases. Currently, during the global program of vaccination against COVID-19 and the possibility of axillary lymphadenopathy after this injection, the correct interpretation of PET/CT images is vitally significant and may create some difficulties. We present a case of increased uptake of [18F]FDG in an axillary lymph node in a PET/CT scan performed 2 days after the Pfizer BioNTech COVID-19 vaccine in a 48-year-old patient newly diagnosed with marginal zone B-cell lymphoma.Copyright © 2023 Via Medica.
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Background: Sydenham chorea, or rheumatic chorea, is a movement disorder that is more prevalent among young people, with a mean age at symptom onset between 8 and 9 years. The condition is more common in females. Sydenham chorea is associated with rheumatic fever and is considered the most common cause of acute chorea in children. We believe that the present case is worth reporting since the occurrence of Sydenham chorea as a post-COVID-19 sequela has not been described in Brazil. Case Presentation: We report here the case of a 14-year-old girl with symptoms of acute chorea that emerged 15 days after treatment resolution of COVID-19 (SARS-CoV-2 or severe acute respiratory syndrome coronavirus 2). Brain computed tomography (CT) and magnetic resonance imaging scans showed no changes, and the laboratory tests revealed no signs of an active infectious process. In contrast, neurological positron-emission tomography/CT showed mild glycolytic hypometabolism in the bilateral mesial frontal region. Administration of an oral anticonvulsant resulted in a marked improvement in her symptoms. Conclusion(s): Despite major efforts of the scientific community for discovering treatments, preventive methods, mechanisms of action, and possible sequelae of SARS-CoV-2, there is still a long way to go to better understand this devastating pathological agent that has affected the global population.Copyright © 2023 Camargo and Morcillo.
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Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.
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Case report Background: Giant cell arteritis (GCA) is an immune-mediated vasculitis affecting large arteries. It has been hypothesized that pathogens including viruses may trigger inflammation within the vessel walls. Human leukocyte antigens' (HLA) genetic studies have previously reported HLA-DR4 (HLA-DRB1* 04 and HLA-DRB1* 01) as susceptibility, and HLA-DR2 (HLA-DRB1* 15 and HLA-DRB1* 16) as protective alleles for GCA. Here we report two cases of large vessel (LV) GCA diagnosed in patients previously suffered from mild coronavirus disese 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2). Case presentation: First case, a 69-year- old male, had a mild COVD-19 three months before the appearance of headache, malaise, and a febrile state associated with extremely increased inflammatory parameters (CRP 2847 mg/dl and IL-6 802.3 pg/ml). Computed tomography examination of the aorta (CTA) and the branches, performed in two occasions six months apart, showed an interesting picture of a migratory arteritis. HLA typing showed: HLA-A* 2,-A* 24;-B* 51,-B* 57;-DRB1* 15,-DRB1* 16;-DQB1* 05,-DQB1* 06;Second case, a 64-year- old female, was evaluated for LV-GCA two months after a mild COVID-19, when she presented with elevated CRP (183mg/dl) and systemic symptoms. Thickening of the ascending aorta and the aortic arch was seen on CTA. Typing of HLA revealed: HLA-A* 2,-A* 11;-B* 27,-B* 35;-DRB1* 14,-DRB1* 15;-DQB1* 05,-DQB1* 06;A whole-body 18F-FDG- PET/ CT performed in both cases revealed inflammation of the ascending, aortic arch, thoracic and abdominal aorta. The first patient had appearance of the inflammatory involvement of the iliac and femoral arteries, while the second patient had an additional pulmonary trunk inflammation. Corticosteroid treatment was introduced in both cases. Due to a progressive inflammatory course of LV-GCA in the first case, the IL-6 inhibitor (tocilizumab) was initiated, leading to a clinical and laboratory improvement. In conclusion, LV-GCA may be considered as an autoimmune disease triggered by SARS-CoV- 2, as one of the broad spectrum of manifestation within the post acute COVID-19. None of the previously known HLA susceptibility alleles for GCA were detected in our patients. In contrast, both patients had DRB1*15 allele, and one of them was DRB1*15/DRB1*16 carrier, suggesting a possibility of losing their protective effect in LV-GCA induced by COVID-19.
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Aim: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/ computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. Method(s): Between November 2020 and May 2021, in this pilot, casecontrol study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59+/-12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. Result(s): There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, p=0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, p=0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho=-0.528, p=0.017 and Spearman's rho=-0.480, p=0.032, respectively), Figure 1. Patients who were scanned less than or equal to 60 days from admission (n=11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, p=0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, p=0.038). There was a significant difference in IAS-TBR between patients scanned <=60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], p=0.036), Figure 2. Conclusion(s): This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post-COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.
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Circulating tumor DNA is a liquid biomarker that offers a highly specific method to assess HPV-associated tumor burden via a blood draw. It has the potential for many clinical applications in cancer care, including prognostication, monitoring treatment response, and surveillance for disease recurrence. In this case report, we present a case of recurrent HPV-associated hypopharyngeal squamous cell carcinoma first detected by circulating tumor HPV DNA that demonstrates the role of circulating tumor HPV DNA tests in posttreatment surveillance and the utility of HPV testing in all HPV-mediated tumors, regardless of subsite.Copyright © 2023 Elsevier Inc.
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Novel coronavirus-19 (COVID-19) variants continue to spread worldwide with the development of highly transmissible strains. Several guidelines addressing management of cancer patients during the COVID-19 pandemic have been published, primarily based upon expert opinion. The COVID-19 pandemic has affected all aspects of breast cancer care including screening, diagnosis, treatment, and long-term follow-up. Recent reports indicate that mRNA COVID-19 vaccines can provoke lymphadenopathy in both cancer patients and healthy individuals. Unilateral axillary lymphadenopathy (UAL) post-COVID-19 vaccination is a challenging presentation for cancer patients because of the potential for misinterpretation as malignancy. The World Health Organization's target to vaccinate 70% of the world's population by mid-2023 is likely to increase the incidence of post-COVID-19 vaccination UAL. In this article, we review the published evidence regarding UAL post-COVID-19 vaccination and present diverse cases of breast cancer patients where false-positive UAL post-COVID-19 vaccination proved to be a therapeutic challenge. The United Arab Emirates (UAE) vaccination program is well ahead of other countries in the world, having accomplished the target of 100% vaccination of the population with at least one dose. Therefore, an increasing number of recently vaccinated patients are likely to present with UAL, detected by surveillance imaging, post-vaccination. We have therefore made recommendations regarding the management of cancer patients with UAL post-COVID-19 vaccination in order to avoid misdiagnosis and unnecessary imaging or invasive biopsy procedures.
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Introduction & Objectives: Urothelial cancer is a lethal disease with a rising incidence. The current imaging modalities for staging, either CT of the chest, abdomen and pelvis or FDG PET/CT, have issues. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG PET is predominantly renally excreted and has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Utilizing 89Zr-TLX250, which is predominantly hepatically cleared, may improve imaging in these scenarios. The aim of this study is to explore the feasibility, safety, and utility of Zirconium-89-Girentuximab (89Zr-TLX250) PET/CT in the accurate staging of bladder and urothelial cancer as compared to FDG PET. Material(s) and Method(s): ZipUp is single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. Following Ethical approval (HREC ID: RGS3940), all participants undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison (Figure 1. Trial Schema). This trial aims to recruit 10 participants undergoing pre-operative staging prior to planned cystectomy and 10 participants with known metastatic disease. The primary endpoint is feasibility defined by the ability to recruit to the target sample size within the study duration. Secondary endpoints are safety, tolerability and sensitivity/specificity in detecting lymph node metastases (pre-cystectomy group) compared with FDG PET/CT. Result(s): Since May 2021, 15 patients consented to participate, but 2 patients subsequently withdrew. 7 patients did not proceed to dose administration and imaging due to COVID-19 pandemic related supply issues of IMP which would have delayed initiation of treatment. 6 patients have been enrolled with imaging performed. . 5 pre-cystectomy staging group . 1 metastatic group Conclusion(s): If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. [Figure presented]Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Over the course of a clinical trial, changes in the practice environment have the potential to reduce internal and external validity and impact change in patient outcomes. Such ''history effects''1 can take the form of changes in standard of care, clinical guidelines and recommendations, new drug/device availability in the marketplace, testing and screening procedures, and, as recently experienced, a global pandemic. Clinical trials conducted over many years are particularly susceptible to history effects. Such effects can impact foundational ability to continue a trial, including clinician equipoise and ability to implement trial interventions, necessitating awareness and action planning. For example, Curtis et al.2 acknowledged challenges with clinical guideline history effects and issued recommendations for addressing them such as consideration of participant wellbeing, stakeholder engagement, safety monitoring, review of guideline and policy changes, and development of rules for protocol changes. This session will explore how four multisite clinical trials conducted with VA Cooperative Studies Program sponsorship and coordination have weathered history effects during prolonged periods of enrollment. Topics to be covered include the implementation of pragmatic designs, monitoring of clinical guidelines, assessing control group treatment conditions, modifying protocols, adjusting quality assurance procedures, refining recruitment pathways, and training site investigators. The speakers, Study Chairs, will describe best practices and provide recommendations for navigating history effects in prolonged multisite clinical trials that can ensure outcomes remain relevant and compelling to inform public health at trial commencement. The CSP 2008/PTXRx study is a pragmatic, randomized, double-blind, placebo-controlled, multicenter clinical trial of Veteran patients with diabetic kidney disease (DKD) examining whether pentoxifylline (PTX), when added to usual care, can delay time to end-stage renal disease or death. Enrollment for the study began in 2019, and it is anticipated that 9 years of follow-up will be required to observe the required number of primary events. Given the long duration of the study, changes in clinical guidelines were anticipated and have occurred, including the approval of new DKD therapies and introduction of a new formula for estimated glomerular filtration rate (eGFR) calculation. In anticipation of these changes, the study design allows for whatever standard of care is extant at any time during the course of the study. PTXR's pragmatic trial design and protocol leverage the VA's research infrastructure and remote platforms allowing the study to be responsive to external changes and to safely continue during a global pandemic. The CSP 596/OPTION study is a randomized, double- blind, multicenter trial of Veteran patients with a first or second recurrent Clostridium difficile infection (CDI) comparing (1) fidaxomicin and (2) vancomycin, followed by a taper and pulse to (3) a standard vancomycin regimen. Since enrollment began in 2016, significant changes in CDI epidemiology and clinical management have impacted the study. The COVID-19 pandemic also resulted in an administrative hold on all trial activity followed by staggered reopening of sites due to variable COVID-19 activity and clinical priorities. Many clinical laboratories switched to algorithms that included free toxin assays in addition to polymerase chain reaction (PCR) tests out of concern for overdiagnosis based on PCR testing alone, reducing the number of potentially enrollable cases. There has been increased empirical vancomycin treatment for recurrent CDI without confirmation by stool testing, a requirement for enrollment, and a recruitment strategy for identifying potential cases. Finally, conflicting clinical guidelines for recurrent CDI has created potential equipoise when considering enrollment. Ongoing educational efforts have been made to clarify the protocol and emphasize the validity of the research question as well as protoco changes to allow safe enrollment and follow-up of participants in the face of the ongoing COVID-19 pandemic. The CSP 2005/VALOR is a phase III randomized, open label, multicenter clinical trial of Veteran patients with operable stage I non-small cell lung cancer that compares stereotactic radiotherapy and anatomic pulmonary resection with a primary outcome measure of overall survival. The study was activated in 2017 and recruitment to the trial has been affected by ongoing changes in public and clinician perceptions about stereotactic radiotherapy and surgery that have interfered with equipoise and willingness of participants to enroll. The study team perpetually addresses this challenge through group conversations with local site investigators, study coordinators, and other research personnel to preserve group equipoise across the study. Since the study's activation, new safety information about stereotactic radiotherapy has emerged necessitating protocol modifications while aiming to preserve internal and external validity. The includes modifying standard operating procedures for the study's centralized quality assurance program that has had to adapt its process to remain contemporary. STARPORT, funded by VA CSRD with CSP collaboration, is a randomized, open label, multicenter clinical trial of Veteran patients with oligorecurrent prostate cancer comparing the effects of standard systemic therapy (SST) alone or with PET-directed local therapy using surgery or radiation. Although enrollment was initiated in 2021, changes are already evident in clinical practice guidelines regarding the use of imaging in workup in this patient population. Shortly before the start of accrual, 18F-DCFPyL PSMA PET/CT received FDA-approval. Consequently, it is being rapidly adopted at the STARPORT VA medical centers and the use of conventional imaging using CT or bone scan prior to PET/CT imaging-part of the original eligibility criteria-quickly is falling out of favor. Furthermore, shortly after the start of enrollment, NCCN guidelines adopted the stance that conventional imaging was no longer required in the setting of PSMA PET/CT imaging, solidifying the transition away from conventional imaging. Thus, the protocol is being amended to remove the requirement for conventional imaging as part of workup for oligorecurrence. In addition, to be generalizable, the study is designed to integrate future PSMA radiotracers that are incorporated into practice as well as changes in SST regimens over the time of the study.
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Melanoma of unknown primary (MUP) was originally defined in 1963 as melanoma in the subcutaneous tissue, lymph nodes or visceral organs without the presence of a cutaneous, ocular or mucosal primary. The incidence of MUP is reported to be between 1% and 8% of all melanomas. MUP can be divided into lymph node involvement only and organ metastases. The aetiology of MUP is elusive. Possibilities proffered include an unrecognized melanoma, a previously excised melanoma that was misdiagnosed as benign, a primary melanoma that has completely regressed or the de novo malignant transformation of an aberrant melanocyte within a lymph node. We report our experience in a single tertiary referral centre. A database of all melanomas diagnosed between January 2018 and December 2021 was analysed for MUP. The total number of melanomas diagnosed in that timeframe was 298. Six patients (three males, three females) were identified as having MUP, with an incidence of 2%. Median age was 63.3 years (range 45-84). One (17%) presented with primary dermal metastatic deposits, 67% (n = 4) presented with isolated lymph node metastases, 0% presented with visceral metastases and 17% (n = 1) presented with isolated brain metastases. All six patients were reviewed by dermatology and ophthalmology. Fifty per cent (n = 3) were reviewed by ENT. One (17%) was referred to gynaecology. No primary melanoma was identified in any of the patients. All patients underwent a positron emission tomography-computed tomography (CT) scan to investigate for further metastases, and all underwent dedicated brain imaging via CT and magnetic resonance imaging. All patients underwent surgical resection of their MUP, and all were reviewed by medical oncology, with 83% (n = 5) undergoing treatment with immunotherapy. There have been no associated deaths to date. In five patients (83%) the MUP was diagnosed in 2021, and one (17%) was diagnosed in 2018. Recent studies have shown the impact of the COVID- 19 pandemic on the presentation of cutaneous melanoma, including an increased Breslow thickness at the time of presentation vs. a similar period pre-COVID-19. Our data indicate an increased rate of MUP presenting after the onset of the COVID-19 pandemic;however, given the low number overall, no conclusions can be drawn. There is no current literature regarding the increased rate of MUP since the COVID-19 pandemic. Further studies are required to investigate this. Recommendations for the evaluation of those with MUP include a full skin examination by a dermatologist and ocular examination to exclude primary melanoma. Patients should undergo imaging of the brain, thorax, abdomen and pelvis to assess disease burden. Referral to otorhinolaryngology can be considered to assess for mucosal melanoma of the nasopharynx. Gynaecology referral should be considered for those with inguinal lymphadenopathy. MUP is rare. Guidelines for the investigation of MUP are currently lacking and are needed to ensure the delivery of consistent evidence-based care for patients.
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Objective: The COVID-19 pandemic has had an impact on health care. In the Netherlands, hospital capacity for non-covid care was limited and population screening temporarily halted. The aim of this study was to investigate the impact of the pandemic on the diagnostic pathway of breast cancer. Method(s): In this study, 48,425 breast cancer patients with a primary breast tumour were selected from the Netherlands Cancer Registry and the Dutch Hospital Data. Patients diagnosed in period January 2020 to July 2021 were divided into six periods, based on the number of hospitalizations due to the COVID-19 pandemic and compared to the same periods in 2017-2019. A t-test was performed to compare the number of diagnosed patients per period. Patient characteristics were compared using chi-squared test. The impact on the procedures performed was analysed using logistic regression. The median time between diagnosis and therapy and the median time between first diagnostic procedure and therapy was analysed using Cox Proportional Hazards Regression. All results were corrected for age, stage and region. Result(s): During the first peak of the pandemic in 2020, significantly fewer patients (-48,2%) have been diagnosed with breast cancer. This decrease is mainly seen in lower stage tumours. Mammography and echography were performed significantly less per patient during the first recovery in 2020 (OR=0.83 and OR=0.85 respectively) compared to 2017-2019. PET-CT was performed significantly more often during the first peak and first recovery in 2020 (OR=1.94 and OR=1.39 respectively). The median time between diagnosis and start of therapy significantly decreased in 2020, during the first peak by 3 days (HR=1.26), during first recovery and second peak by 1 day (HR=1.04 and HR=1.16 respectively). The median time between first diagnostic procedure and start of therapy significantly decreased in 2020, during the first peak by 4 days (HR=1.25), during the first recovery by 1 day (HR=1.04) and during the second peak by 2 days (HR=1.13). Conclusion(s): The decreased number of diagnosis was related to the temporary halt of the screening. Diagnostics for early stage tumours was limited and for PET-CT was performed more often reflecting the change in proportion of higher stage. A reduced time of the diagnostic pathway is the result of less hospitalized patients with cancer and the effort on keeping the oncology care in place. (Table Presented).
ABSTRACT
Background Legionella pneumonia is a rare cause of myocarditis. Case 64-y.o male with CAD and PCI to LAD, DM and HTN presented to ER with mental status changes. On exam he was febrile and hypoxic.Presenting rhythm was Afib with frequent bouts of sustained and non-sustained stable posteroseptal VT treated with amiodarone and mexilitene. With right lung infiltrate on CXR and elevated WBC count, antibiotics were initiated for pneumonia. SARS COV-2 Ag and Influenza A & B was negative. Urine Ag for legionella was positive and was promptly treated with Levofloxacin. Coronary angiogram prior to discharge showed non-obstructive CAD. Decision-making Legionnaires' disease with myocarditis was suspected. Patient underwent CMR with late gadolinium enhancement (LGE) and Rest 82Rb perfusion and 18F-FDG PET/CT with high-fat dietary preparation scan for evaluation of legionella myocarditis. CMR revealed LVEF of 46%, with LGE and PET findings as described in the Figure. He was initiated on solumedrol for ongoing inflammation after completion of antibiotic therapy for Legionella pneumonia. Conclusion Our case highlights a systematic approach to differential diagnosis and use of multimodality imaging in legionella myocarditis presenting with dual chamber arrhythmia. There was good correlation between LGE inflammation/scar location and origin of VT, as well as active inflammation demonstrated by FDG PET imaging. The patient was successfully treated with antibiotics, steroids and anti-arrhythmic drugs. [Formula presented]Copyright © 2023 American College of Cardiology Foundation
ABSTRACT
Sinonasal cancer accounts for roughly only 3% of upper respiratory tract malignancies and generally presents as a primary malignancy. Although extremely rare, the sinonasal cavity is also a known location for metastasis, with 8% of these cases originating from primary breast cancer. When attempting to differentiate primary disease from metastasis, immunohistochemical analyses play a crucial role in reaching the correct diagnosis. To date, there are a handful of reports describing metastasis involving the paranasal sinuses but even fewer reporting primary sinonasal cancer with coexisting primary malignancy. Here we present a case of primary sinonasal adenocarcinoma in the setting of a long-standing history of breast cancer. The patient, a 73-year-old female, was diagnosed with T1cN1aM0, progesterone receptor positive and estrogen receptor negative ductal carcinoma in situ of the left breast in November 2019. She subsequently underwent bilateral mastectomy and treated with 3 cycles of chemotherapy and anastrozole, which were both discontinued due to intolerance. Of note, in March 2019, MRI of the head incidentally found a 3 x 2 cm mass in right nasal cavity extending into ethmoid sinus. One year later, she presented with mild right sided nasal obstruction and drainage, and biopsy revealed squamous and respiratory mucosa with chronic inflammation. The patient elected to cancel initial surgical resection of the mass due to the COVID-19 pandemic. The patient returned in March 2022 with complaints of eye pressure, double vision, headaches, and worsening nasal obstruction. PET/CT scan was negative for distant metastasis but demonstrated increased uptake in sinus cavity. MRI showed a larger 5 x 3.7 cm mass impressing on medial inferior margins of orbit. Imaging also suggested evidence of dehiscence of lamina and irregular neo-osteogenesis of the skull base. She underwent approach and resection of the mass with histology demonstrating a well differentiated, low grade non-intestinal mucinous adenocarcinoma. Immunohistochemistry was positive for pankeratin and CK7, favoring a primary sinonasal origin. It was estrogen receptor negative and negative for GATA3, a sensitive and fairly specific stain in mammary carcinoma. Adjuvant radiation was recommended postoperatively, however the patient declined this therapy. This case highlights the role of immunohistochemistry to discriminate a new primary cancer from metastasis in patients with a history of breast cancer. Clinically, patients with sinonasal metastasis can present with symptoms ranging from unilateral nasal obstruction, facial pain, diplopia, and decreased vision. On imaging, suspicion of malignancy is raised when there is evidence of destruction of bony boundaries and invasion of surrounding tissues such as the orbit and anterior skull base, as found in our patient. Notably, metastasis to the paranasal sinuses can mimic a primary cancer of the nasal cavity, with both tumors showing epithelial differentiation. However, primary tumors often show neoplastic changes in the overlying respiratory epithelium and do not express estrogen receptor, progesterone receptor, or HER2 positivity, which are known to be correlated with breast cancer. In this setting, GATA3 and estrogen receptor negativity allowed us to diagnose primary nasal cancer more confidently. Therefore, clinicians should be aware of metastatic disease and expand immunohistochemistry panels when appropriate.