The Delay and Costs of Diagnosing Systemic Vasculitis in a Tertiary-Level Clinic

Introduction The diagnosis of systemic vasculitis is a challenge because of the heterogeneity of clinical manifestations. The aim of this study is to analyze the diagnostic delay in systemic vasculitis, the total costs during the first year of care, and how the diagnostic delay affects the costs in a tertiary health care facility. Methods Patients with a new diagnosis of systemic vasculitis between 2010 and 2018 were identified from hospital records. The diagnostic delay and health care costs were evaluated during the diagnostic period and within 12 months after the first contact with tertiary health care. Vasculitis-related costs were recorded as true costs charged. A total of 317 patients fulfilled the study criteria. The diagnoses were grouped into three clinically relevant groups: IgA vasculitis and other small-vessel vasculitis (n = 64), ANCA-associated vasculitis (AAV) (n = 112), and large-vessel vasculitis (LVV) (n = 141). Results The diagnostic delay from the first referral to tertiary-level clinic was shortest in the LVV group and longest in the AAV group. Total costs during the diagnostic period were the highest in the AAV group (median = €6754 [IQR €8812]) and lowest in the LVV group (median = €3123 [IQR €4517]), p s = 0.38, p s = 0.34, p p Conclusions There is a substantial diagnostic delay that correlates significantly with the costs in tertiary-level health care when diagnosing systemic vasculitis.</div

Granulocyte colony-stimulating factor- and chemotherapy-induced large-vessel vasculitis : six patient cases and a systematic literature review

Objective. Patients receiving chemotherapy are prone to neutropoenic infections, presenting with non-specific symptoms such as a high fever and elevated inflammatory parameters. Large-vessel vasculitis (LVV) may have a similar clinical presentation and should be included in differential diagnostics. A few published case reports and adverse event reports suggest a causal association between LVV and the use of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. Our objective was to evaluate the relationship between LVV, G-CSF and chemotherapy. Methods. Between 2016 and 2018, we identified six patients in Finland with probable drug-induced LVV associated with G-CSF and chemotherapy. All six patients had breast cancer. A systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for cancer, chemotherapy, G-CSF and LVV. Results. The literature search identified 18 similar published case reports, of which most were published after 2014. In all patients combined (n = 24), the time delay from the last drug administration to the LVV symptoms was on average 5 days with G-CSF (range = 1-8 days) and 9 days with chemotherapy (range = 1-21 days). Common symptoms were fever (88%), neck pain (50%) and chest pain (42%). Based on imaging, 17/24 (71%) had vascular inflammation in the thoracic aorta and supra-aortic vessels, but 5/24 (21%) reportedly had inflammation limited to the carotid area. Conclusion. This review suggests that LVV may be a possible serious adverse event associated with G-CSF and chemotherapy. Successful management of drug-induced LVV requires early identification, through diagnostic imaging, and discontinuation of the drug.Peer reviewe

Prosthetic Valve Candida Endocarditis: A Case Report with 18F-FDG-PET/CT as Part of the Diagnostic Workup

Diagnosis of Candida spp. infective endocarditis (IE) is challenging, and diagnostic delays are common. We describe two patients with Candida spp. prosthetic valve endocarditis (PVE) and 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) as a part of diagnostic workup. We also refer to 5 other cases we found from the published literature. These cases highlight that 18F-FDG-PET/CT can improve diagnostic accuracy in prosthetic valve Candida endocarditis

The validity of systemic sclerosis diagnoses in two university hospitals in Finland

Objective: This study aimed to determine the validity of systemic sclerosis (SSc) diagnoses in Finnish university hospitals.Method: Electronic medical records for 385 patients with a registered diagnosis of SSc (ICD-10 code M34) in two Finnish university hospitals from 2008 to 2018 were reviewed to assess whether each patient's diagnosis was correct.Results: The positive predictive value (PPV) of a diagnosis of SSc was 0.66 when fulfilment of the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SSc was required; the PPV was 0.75 if patients meeting the 2001 LeRoy and Medsger classification criteria for early SSc were also included. When a diagnosis of SSc was made in a department of rheumatology, the PPV was 0.78, and 0.90 when including patients with early SSc. For the more specific diagnosis of limited cutaneous SSc (lcSSc), the PPV was 0.80, and 0.95 when including early SSc. For an lcSSc diagnosis made in rheumatology, the PPV was 0.81, and 0.97 with early SSc included.Conclusion: These results demonstrate that in these two Finnish university hospitals, the diagnostic validity of a diagnosis of SSc was good if it was diagnosed in the department of rheumatology. For a more specific diagnosis of lcSSc, the most prevalent form of SSc in Finland, the validity was good even when registered in any department.</p

Granulocyte colony-stimulating factor- and chemotherapy-induced large-vessel vasculitis: six patient cases and a systematic literature review

Patients receiving chemotherapy are prone to neutropoenic infections, presenting with non-specific symptoms such as a high fever and elevated inflammatory parameters. Large-vessel vasculitis (LVV) may have a similar clinical presentation and should be included in differential diagnostics. A few published case reports and adverse event reports suggest a causal association between LVV and the use of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. Our objective was to evaluate the relationship between LVV, G-CSF and chemotherapy.MethodsBetween 2016 and 2018, we identified six patients in Finland with probable drug-induced LVV associated with G-CSF and chemotherapy. All six patients had breast cancer. A systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for cancer, chemotherapy, G-CSF and LVV.ResultsThe literature search identified 18 similar published case reports, of which most were published after 2014. In all patients combined (n = 24), the time delay from the last drug administration to the LVV symptoms was on average 5 days with G-CSF (range = 1–8 days) and 9 days with chemotherapy (range = 1–21 days). Common symptoms were fever (88%), neck pain (50%) and chest pain (42%). Based on imaging, 17/24 (71%) had vascular inflammation in the thoracic aorta and supra-aortic vessels, but 5/24 (21%) reportedly had inflammation limited to the carotid area.ConclusionThis review suggests that LVV may be a possible serious adverse event associated with G-CSF and chemotherapy. Successful management of drug-induced LVV requires early identification, through diagnostic imaging, and discontinuation of the drug.</div

Head-to-Head Comparison of 68Ga-Citrate and 18F-FDG PET/CT for Detection of Infectious Foci in Patients with Staphylococcus aureus Bacteraemia

Purpose. This study evaluated the potential of 68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with Staphylococcus aureus bacteraemia by comparing it with 2-[18F]fluoro-2-deoxy--glucose (18F-FDG) PET/CT. Methods. Four patients admitted to hospital due to S. aureus bacteraemia underwent both 18F-FDG and 68Ga-citrate whole-body PET/CT scans to detect infectious foci. Results. The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between 18F-FDG and 68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both 18F-FDG (maximum standardised uptake value [SUVmax 6.0 ± 1.0] ) and 68Ga-citrate (SUVmax 6.8 ± 3.5, P = 0.61). Three patients had soft tissue infectious foci, with more intense 18F-FDG uptake (SUVmax 6.5 ± 2.5) than 68Ga-citrate uptake (SUVmax 3.9 ± 1.2, P = 0.0033). Conclusions. Our small cohort of patients with S. aureus bacteraemia revealed that 68Ga-citrate PET/CT is comparable to 18F-FDG PET/CT for detection of osteomyelitis, whereas 18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.</p

Head-to-Head Comparison of 68

Purpose. This study evaluated the potential of 68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with Staphylococcus aureus bacteraemia by comparing it with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT. Methods. Four patients admitted to hospital due to S. aureus bacteraemia underwent both 18F-FDG and 68Ga-citrate whole-body PET/CT scans to detect infectious foci. Results. The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between 18F-FDG and 68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both 18F-FDG (maximum standardised uptake value [SUVmax] 6.0±1.0) and 68Ga-citrate (SUVmax  6.8±3.5, P=0.61). Three patients had soft tissue infectious foci, with more intense 18F-FDG uptake (SUVmax  6.5±2.5) than 68Ga-citrate uptake (SUVmax  3.9±1.2, P=0.0033). Conclusions. Our small cohort of patients with S. aureus bacteraemia revealed that 68Ga-citrate PET/CT is comparable to 18F-FDG PET/CT for detection of osteomyelitis, whereas 18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci

The Clinical Impact of Using 18F-FDG-PET/CT in the Diagnosis of Suspected Vasculitis: The Effect of Dose and Timing of Glucocorticoid Treatment

18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body 18F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased 18F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in 18F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, ), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, ) compared to 18F-FDG-PET/CT-negative patients. Vasculitis patients with a positive 18F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative 18F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, ). We found that 18F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. 18F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.</p

68Ga-Citrate Positron Emission Tomography of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy males. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with Good Manufacturing Practices. Six healthy males (age 41 ± 12 years, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging and the radioactivity concentration was measured with a gamma counter. Urinary voids were collected and measured. The Medical Internal Radiation Dose (MIRD) bladder-voiding model with a 3.5 hour voiding interval was used. A model using a 70 kg adult male and MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM 2.0 software. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3 hour measuring period. Although radioactivity excretion via urine was rather slow (biological half-time, 69 ± 24 hours), the highest decay-corrected concentrations in urinary bladder contents were measured at 90 and 180 minute time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose of 0.077 ± 0.008 mSv/MBq. The mean effective dose (ICRP 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200 MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.</p