Fever of Unknown Origin, a Vascular Event, and Immunosuppression in Tick-Endemic Areas: Think About Neoehrlichiosis.

Three patients were referred to our hospital because of fever of unknown origin (FUO) and thrombosis or thrombophlebitis. All of them had been under immunosuppression (IS) with rituximab. Intensive diagnostics for FUO and blood cultures remained negative. Finally, the association of fever, immunosuppression, and a vascular event led to the suspicion of Candidatus Neoehrlichia mikurensis (CNM) infection. The diagnosis was confirmed by species-specific polymerase chain reaction (PCR) in the peripheral blood. Therapy with doxycycline or rifampicin led to the resolution of the disease. A liver biopsy was performed in one patient due to hepatomegaly and elevated liver enzymes demonstrating hemophagocytosis. To our knowledge, this is the first histopathological study of liver tissue in CNM infection. The evidence of hemophagocytosis raises the question of whether symptomatic CNM infection might be in part related to host inflammatory and immune responses.

Discordance in the diagnostic assessment of vulnerable plaques between radiofrequency intravascular ultrasound versus optical coherence tomography among patients with acute myocardial infarction: insights from the IBIS-4 study.

We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness < 65 µm. The two modalities were matched based on anatomical landmarks using a dedicated matching software. Using grayscale IVUS, we identified 276 lesions at baseline (N = 146) and follow-up (N = 130). Using RF-IVUS, 208 lesions (75.4%) were classified as TCFA. Among them, OCT identified 14 (6.7%) TCFA, 60 (28.8%) thick-cap fibroatheroma (ThCFA), and 134 (64.4%) non-fibroatheroma. All OCT-TCFA (n = 14) were confirmed as RF-TCFA. The concordance rate between RF-IVUS and OCT for TCFA diagnosis was 29.7%. The reasons for discordance were: OCT-ThCFA (25.8%); OCT-fibrous plaque (34.0%); attenuation due to calcium (23.2%); attenuation due to macrophage (10.3%); no significant attenuation (6.7%). There was a notable discordance in the diagnostic assessment of TCFA between RF-IVUS and OCT. The majority of RF-derived TCFA were not categorized as fibroatheroma using OCT, while all OCT-TCFA were classified as TCFA by RF-IVUS.ClinicalTrials.gov Identifier NCT00962416.

Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study.

AIMS: Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery's global remodelling as reference. METHODS AND RESULTS: Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (-0.67 vs. -0.38 vs. -0.002 mm2; P < 0.001) and lumen area (-0.82 vs. -0.09 vs. 0.40 mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [-0.80% (-1.41 to -0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (-6.14% vs. -0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up. CONCLUSION: Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.

Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study.

OBJECTIVES: This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. BACKGROUND: OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. METHODS: In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. RESULTS: At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 µm to 87.9 ± 38.1 µm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. CONCLUSIONS: In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.