Large Plaques Research Articles

Impact of dietary choline on lipid metabolism and atherosclerosis development in apoEKO mice deficient or overexpressing apolipoprotein A-I: Selected Abstract - XVI SITeCS Congress

TMAO, a metabolite of dietary choline, is considered a pro-atherogenic molecule for its ability to interfere with the reverse cholesterol transport, in which apolipoprotein A-I and HDL play a key role. In the present work it was evaluated how TMAO impacts on the development of atherosclerosis in mice with different levels of apoA-I/HDL. Mice deficient in both murine apoA-I and apoE (DKO) and DKO mice overexpressing human apoA-I (DKO/hA-I), characterized by extremely low or high plasma HDL levels respectively, were fed for 16 weeks two standard rodent diets, differing only in their choline content (0.09% or 1.2%). At the end of the dietary treatment, atherosclerosis development was quantified at the aortic sinus, targeted plasma metabolomics was performed, and gene expression was evaluated in liver, duodenum, jejunum and ileum. With both diets, DKO mice developed much larger plaques than DKO/hA-I mice. High-choline diet increased plasma TMAO levels in both genotypes. Interestingly, a worsening of plaque development by high choline diet occurred in DKO/hA-I mice only (0.057±0.048 mm2 vs 0.0988±0.064 mm2, p<0.01). Plasma metabolomics indicated that choline supplementation, only in the presence of HDL, significantly increased the concentration of some ceramide species in addition to several markers of impaired kidney function. High-choline diet increased the hepatic gene expression of Fmo1 and Fmo2 in DKO/hA-I, whereas the expression of Scarb1 was lower in DKO/hA-I compared to DKO mice, regardless of the dietary treatment. Intestinal expression of genes involved in inflammatory response and in lipid metabolism was comparable between genotypes and was not modified by choline supplementation. In conclusion, high choline diet increased plasma TMAO concentration in both genotypes, but affected atherosclerosis development, plasma metabolome and hepatic gene expression only in high HDL mice. Intestinal gene expression was not affected neither by genotype nor by dietary choline content.

Culprit Plaques of Large Parent Arteries, Rather than Cerebral Small Vessel Disease, Contribute to Early Neurological Deterioration in Stroke Patients with Intracranial Branch Atheromatous Disease

Introduction: Intracranial branch atheromatous disease (BAD) has been applied to occlusions that occur at the origin of large caliber penetrating arteries due to the microatheromas or large parent artery plaques. This study aimed to explore the association between culprit plaques of large parent arteries, neuroimaging markers of cerebral small vessel disease (CSVD), and the risk of early neurological deterioration (END) in stroke patients with BAD. Methods: A total of 97 stroke patients with BAD in the vascular territories of the lenticulostriate arteries or paramedian pontine arteries, diagnosed using high-resolution magnetic resonance imaging, were prospectively recruited in this observational study. A culprit plaque in the middle cerebral artery was defined as the only arterial plaque on the ipsilateral side of an infarction visible on diffusion-weighted imaging. A culprit plaque in the basilar artery (BA) was identified when it was observed within the same axial slices of an infarction or on the adjacent upper or lower slice, whereas a plaque within the BA located in the ventral region was considered non-culprit. If more than one plaque was present in the same vascular territory, the most stenotic plaque was chosen for the analysis. Four CSVD neuroimaging markers, including white matter hyperintensity, lacunes, microbleeds, and enlarged perivascular spaces, were evaluated in accordance with the total CSVD score. The associations between neuroimaging features of lesions within large parent arteries, neuroimaging markers of CSVD, and the risk of END in stroke patients with BAD were investigated using logistic regression analysis. Results: END occurred in 41 stroke patients (42.27%) with BAD. The degree of large parent artery stenosis (p < 0.001), culprit plaques of large parent arteries (p < 0.001), and plaque burden (p < 0.001) were significantly different between the END and non-END groups in stroke patients with BAD. In logistic regression analysis, culprit plaques of large parent arteries (odds ratio, 32.258; 95% confidence interval, 4.140–251.346) were independently associated with the risk of END in stroke patients with BAD. Conclusions: Culprit plaques of large parent arteries could predict the risk of END in stroke patients with BAD. These results suggest that lesions in the large parent arteries, rather than damage to the cerebral small vessels, contribute to END in stroke patients with BAD.

Identification of vulnerable non-culprit lesions by coronary computed tomography angiography in patients with chronic coronary syndrome and diabetes mellitus.

Among patients with diabetes mellitus (DM) and chronic coronary syndrome (CCS), non-culprit lesions (NCLs) are responsible for a substantial number of future major adverse cardiovascular events (MACEs). Thus, we aimed to establish the natural history relationship between adverse plaque characteristics (APCs) of NCLs non-invasively identified by coronary computed tomography angiography (CCTA) and subsequent MACEs in these patients. Between January 2016 and January 2019, 523 patients with DM and CCS were included in the present study after CCTA and successful percutaneous coronary intervention (PCI). All patients were followed up for MACEs (the composite of cardiac death, myocardial infarction, and unplanned coronary revascularization) until January 2022, and the independent clinical event committee classified MACEs as indeterminate, culprit lesion (CL), and NCL-related. The primary outcome was MACEs arising from untreated NCLs during the follow-up. The association between plaque characteristics detected by CCTA and primary outcomes was determined by Marginal Cox proportional hazard regression. Overall, 1,248 NCLs of the 523 patients were analyzed and followed up for a median of 47 months. The cumulative rates of indeterminate, CL, and NCL-related MACEs were 2.3%, 14.5%, and 20.5%, respectively. On multivariate analysis, NCLs associated with recurrent MACEs were more likely to be characterized by a plaque burden >70% [hazard ratio (HR), 4.35, 95% confidence interval (CI): 2.92-6.44], a low-density non-calcified plaque (LDNCP) volume >30 mm3 (HR: 3.40, 95% CI: 2.07-5.56), a minimal luminal area (MLA) <4 mm2 (HR: 2.30, 95% CI: 1.57-3.36), or a combination of three APCs (HR: 13.69, 95% CI: 9.34-20.12, p < 0.0001) than those not associated with recurrent MACEs. Sensitivity analysis regarding all indeterminate MACEs as NCL-related ones demonstrated similar results. In DM patients who presented with CCS and underwent PCI, half of the MACEs occurring during the follow-up were attributable to recurrence at the site of NCLs. NCLs responsible for unanticipated MACEs were frequently characterized by a large plaque burden and LDNCP volume, a small MLA, or a combination of these APCs, as determined by CCTA.

Characterizing morphologic subtypes of high-grade serous ovarian cancer by CT: a retrospective cohort study

ObjectiveA novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features...

Towards a Diagnostic Tool for Turtle Ootaxonomy: Investigation of Microstructural Differences in the Eggshells of Australian Freshwater Turtles

Researchers frequently encounter turtle nests after the nest has been raided, finding only eggshell fragments that are difficult to identify. Valuable information on the breeding biology and needs of different species might still be collected from these nests if remains could be confidently assigned to a particular species. However, this can be difficult if there are multiple turtle species nesting within an area at a given time, and gross-scale characteristics such as egg size and shape are no longer available due to damage. This study examined eggshell microstructure, by scanning electron microscopy (SEM), among multiple species of freshwater turtle eggshell fragments, with the aim of potentially developing a diagnostic tool for species identification. Eggshell fragments were collected from known sources of four species of turtle native to eastern Australia: Eastern Long-necked Turtle (Chelodina longicollis), Murray River Turtle (Emydura macquarii), Bell's Turtle (Myuchelys bellii), and Bellinger River Turtle (M. georgesi). Fragments were scanned and analyzed for microstructural and ultrastructural features, and measured for differences in feature size across species. Central plaque diameter emerged as a potential diagnostic feature for separating species, with longneck turtle eggshells having no visible plaques, Murray River Turtle eggshells having relatively small mean plaque size (19.8 µm ± 10.28 SD), while Bell's Turtle (43.5 µm ± 14.16 SD) and Bellinger River Turtle eggshells (41.9 µm ± 15.41 SD) had relatively large plaques with little overlap between genera. Other measured features (shell unit size, basal knob size, and shell unit density) significantly differed in means among species but overlapped in range, or showed a lack of statistical difference, likely preventing the technique being definitive with a single measure. Some of this variance may be due to inherent confounding factors, such as the replicability of fragment preparation, condition of eggshells, and stage of embryonic development at the time of collection. These results suggest that use of measurements of microstructural features has promise as a means for distinguishing the provenance of eggshell fragments, and further investigation is warranted to develop site-specific protocols for use as a diagnostic tool for turtle ootaxonomy.

Ergothioneine, a dietary antioxidant improves amyloid beta clearance in the neuroretina of a mouse model of Alzheimer's disease.

Ergothioneine (Ergo) is a naturally occurring dietary antioxidant. Ergo uptake is dependent on the transporter, organic cation transporter novel-type 1 (OCTN1) distribution. OCTN1 is highly expressed in blood cells (myeloid lineage cells), brain and ocular tissues that are likely predisposed to oxidative stress. Ergo may protect the brain and eye against oxidative damage and inflammation, however, the underlying mechanism remains unclear. Amyloid beta (Aβ) clearance is a complex process mediated by various systems and cell types including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Impaired Aβ clearance is a major cause for Alzheimer's disease (AD). Here we investigated neuroretinas to explore the neuroprotective effect of Ergo in a transgenic AD mouse model. Age-matched groups of Ergo-treated 5XFAD, non-treated 5XFAD, and C57BL/6J wildtype (WT controls) were used to assess Ergo transporter OCTN1 expression and Aβ load along with microglia/macrophage (IBA1) and astrocyte (GFAP) markers in wholemount neuroretinas (n = 26) and eye cross-sections (n = 18). Immunoreactivity was quantified by fluorescence or by semi-quantitative assessments. OCTN1 immunoreactivity was significantly low in the eye cross-sections of Ergo-treated and non-treated 5XFAD vs. WT controls. Strong Aβ labeling, detected in the superficial layers in the wholemounts of Ergo-treated 5XFAD vs. non-treated 5XFAD reflects the existence of an effective Aβ clearance system. This was supported by imaging of cross-sections where Aβ immunoreactivity was significantly low in the neuroretina of Ergo-treated 5XFAD vs. non-treated 5XFAD. Moreover, semi-quantitative analysis in wholemounts identified a significantly reduced number of large Aβ deposits or plaques, and a significantly increased number of IBA1(+)ve blood-derived phagocytic macrophages in Ergo-treated 5XFAD vs. non-treated 5XFAD. In sum, enhanced Aβ clearance in Ergo-treated 5XFAD suggests that Ergo uptake may promote Aβ clearance possibly by blood-derived phagocytic macrophages and via perivascular drainage.

Resuscitated sudden cardiac arrest related to intraplaque haemorrhage and coronary artery spasm.

A 72-year-old man with a history of chronic kidney disease, dyslipidaemia, and hypertension felt chest tightness after walking uphill and sat down to rest. Shortly thereafter, he suddenly collapsed, and cardiopulmonary resuscitation was started by a nearby family member. The initial electrocardiogram waveform was ventricular fibrillation, which was restored to sinus rhythm with an automated external defibrillator. He was transported to our hospital. No significant electrocardiographic changes, but positive serum troponin was observed on arrival. Emergency coronary angiography was performed, revealing a moderate stenosis in the proximal left anterior descending coronary artery (Panel A) which was functionally significant (Panel B). Optical coherence tomography showed a large eccentric plaque with a confined low-intensity plaque with strong signal attenuation (Panel C) and some areas of low intensity and low attenuation (Panel D), highly suggestive of intraplaque haemorrhage (IPH) (see Supplementary data online, Video S1).1 A stent implantation was subsequently performed (Panel E). On the ninth day of hospitalization, an acetylcholine provocation test was performed for the right coronary artery and severe diffuse coronary spasm was induced (Panels F and G) accompanied by chest tightness and ST elevation on electrocardiogram, leading to a diagnosis of coronary spastic angina.

Charged multivesicular body protein 4b forms complexes with gap junction proteins during lens fiber cell differentiation.

Charged multivesicular body protein 4b (CHMP4B) is a core sub-unit of the endosomal sorting complex required for transport III (ESCRT-III) machinery that serves myriad remodeling and scission processes of biological membranes. Mutation of the human CHMP4B gene underlies rare forms of early-onset lens opacities or cataracts, and CHMP4B is required for lens growth and differentiation in mice. Here, we determine the sub-cellular distribution of CHMP4B in the lens and uncover a novel association with gap junction alpha-3 protein (GJA3) or connexin 46 (Cx46) and GJA8 or Cx50. Immunofluorescence confocal microscopy revealed that CHMP4B localized to cell membranes of elongated fiber cells in the outer cortex of the lens-where large gap junction plaques begin to form-particularly, on the broad faces of these flattened hexagon-like cells in cross-section. Dual immunofluorescence imaging showed that CHMP4B co-localized with gap junction plaques containing Cx46 and/or Cx50. When combined with the in situ proximity ligation assay, immunofluorescence confocal imaging indicated that CHMP4B lay in close physical proximity to Cx46 and Cx50. In Cx46-knockout (Cx46-KO) lenses, CHMP4B-membrane distribution was similar to that of wild-type, whereas, in Cx50-KO lenses, CHMP4B localization to fiber cell membranes was lost. Immunoprecipitation and immunoblotting analyses revealed that CHMP4B formed complexes with Cx46 and Cx50 in vitro. Collectively, our data suggest that CHMP4B forms plasma membrane complexes, either directly and/or indirectly, with gap junction proteins Cx46 and Cx50 that are often associated with "ball-and-socket" double-membrane junctions during lens fiber cell differentiation.

Large Frontal Defect Reconstructed with a Suprafascial Anterolateral Thigh Flap and Brow Suspension with a Fascia Lata Frontalis Sling

A 60-year-old gentleman presented with a single, dark scaly lesion over the forehead for the past 8 years. It started as a small plaque spontaneously, insidious in onset and gradually progressed to the present size. There was no history of trauma, pain or bleeding from the lesion. No history of similar complaints in the family. On examination, there was a large hyperpigmented plaque measuring 15 x 10 cm with well-defined margins and rolled-out edges with ulceration 2 x 0.5cm at the centre. (Fig. 1) Edge wedge biopsy from the lesion revealed a proliferation of basaloid cells which showed features consistent with basal cell carcinoma - atypical mitosis and peripheral palisading. After obtaining anaesthetic fitness, we proceeded with wide local excision with 1cm margin done by the surgical oncology team. (Fig. 2) We then followed by reconstruction of the frontalis sling using fascia lata and covered the defect with a free suprafascial ALT flap with superficial temporal as the recipient artery as an end-to-end anastomosis. (Fig. 3, 4) The donor site was resurfaced with SSG. The histopathology report was consistent with basal cell carcinoma without any perineural involvement. The early postoperative period showed the flap supple and soft with no oedema. (Fig. 5) On regular follow-up, the flap was well settled with good cosmesis. (Fig. 6)

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study

BackgroundThis study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre–percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. Methods52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. ResultsOf 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65–17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11–23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53–21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. ConclusionsThere is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification.Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Biological Properties of 12 Newly Isolated Acinetobacter baumannii-Specific Bacteriophages.

Infections with the opportunistic Gram-negative bacterium Acinetobacter baumannii pose a serious threat today, which is aggravated by the growing problem of multi-drug resistance among bacteria, caused by the overuse of antibiotics. Treatment of infections caused by antibiotic-resistant A. baumannii strains with the use of phage therapy is not only a promising alternative, but sometimes the only option. Therefore, phages specific for clinical multi-drug resistant A. baumannii were searched for in environmental, municipal, and hospital wastewater samples collected from different locations in Poland. The conducted research allowed us to determine the biological properties and morphology of the tested phages. As a result of our research, 12 phages specific for A. baumannii, 11 of which turned out to be temperate and only one lytic, were isolated. Their lytic spectra ranged from 11 to 75%. The plaques formed by most phages were small and transparent, while one of them formed relatively large plaques with a clearly marked 'halo' effect. Based on Transmission Electron Microscopy (TEM), most of our phages have been classified as siphoviruses (only one phage was classified as a podovirus). All phages have icosahedral capsid symmetry, and 11 of them have a long tail. Optimal multiplicity of infections (MOIs) and the adsorption rate were also determined. MOI values varied depending on the phage-from 0.001 to 10. Based on similarities to known bacteriophages, our A. baumannii-specific phages have been proposed to belong to the Beijerinckvirinae and Junivirinae subfamilies. This study provides an additional tool in the fight against this important pathogen and may boost the interest in phage therapy as an alternative and supplement to the current antibiotics.

Summary of the methods of restraining the decline of evaluation accuracy on the degree of coronary stenosis caused by coronary artery calcification at the present stage

Coronary computed tomography angiography (CCTA), as a non-invasive method to detect the degree of coronary artery stenosis, is often used as a primary screening method for asymptomatic patients, but the performance in positive predictive value often fluctuates. The main reason is the partial volume effect caused by large area coronary artery calcification plaque, which limits the clinical application of CCTA. This article summarizes the methods of suppressing evaluation errors on the degree of stenosis caused by coronary artery calcification, in order to provide some reference for clinical workers in the treatment of patients with severe calcification.

The prevalence of gingivitis and related risk factors in schoolchildren aged 6–12 years old

BackgroundAccording to epidemiological studies, gingivitis is a common disease. However, its morbidity, considerably varies among individual. This study aimed to investigate the epidemiological characteristics of gingivitis, including prevalence, severity, intraoral distribution, and associated risk factors, in children aged 6–12 years in Jinzhou, China.MethodsA multistage, whole-group, randomized sample of 2880 children aged 6–12 years in Jinzhou City, China, was selected and clinically examined. Each selected child completed a questionnaire on sociodemographic factors and oral health behaviors in cooperation with the investigator and teacher. Gingival bleeding refers to the bleeding of 10% or more teeth under the condition of ingivitis. Gingivitis was further categorized into localized gingivitis (30% ≥ number of teeth positive for gingival bleeding ≥ 10%) and generalized gingivitis (number of positive for gingival bleeding > 30%). The score of gingival bleeding was recorded using the Gingival Index.ResultsThe prevalence of gingivitis in children aged 6–12 years in Jinzhou was 28.58%, including 701 cases of localized gingivitis (24.3%) and 122 cases of generalized gingivitis (4.2%). There were 429 cases (28.3%) of gingivitis in males and 394 cases (28.9%) in females, with no statistically significant difference in prevalence between males and females (P > 0.05). Chi-square tests and binary logistic regression analysis showed that aging, dental calculus, plaque, and dental crowding were significantly associated with a high prevalence of gingivitis.ConclusionsOur study showed that dental calculus, large amount dental plaque, poor oral health behavior, and oral health awareness are associated with the prevalence of gingivitis and maintaining children's oral health requires professional guidance and regular preventive care.

An asymmetric morbilliform eruption in an adult male

An asymmetric morbilliform eruption in an adult male

La cytosteatonecrose du nouveau-ne au chu de Conakry: a propos d’une nouvelle observation

Cytosteatonecrosis is an acute condition of unknown pathogenesis that occurs in the first weeks of extra-uterine life. It presents clinically in the form of a large plaque, indurated and sometimes nodular. It often sits on the trunk, buttocks and thighs (root of the limbs). The course of cytosteatonecrosis is benign but sometimes enamelled with complications such as hypercalcemia and metabolic disorders. The rarity of this affection would be justified by the ignorance of the cutaneous signs. We report here a case of neonatal cytosteatonecrosis remarkable for the delay in diagnosis and the efficacy of low-dose corticosteroid therapy.

RARE CUTANEOUS ADVERSE REACTION TO ROUTINE IMMUNIZATIONS LEADING TO HYPER IGE SYNDROME (HIES) DIAGNOSIS

<h3>Introduction</h3> While injection site reactions are common following immunizations, botryomycosis is an uncommon chronic granulomatous bacterial infection that develops in an area of prior injury, typically the skin. Hyper IgE Syndrome (HIES) is a rare primary immunodeficiency characterized by bacterial infections, elevated IgE and cutaneous manifestations; most commonly eczema, mucocutaneous candidiasis and cold abscesses. This case describes the development of a botryomycosis infection following routine two-month vaccinations, leading to HIES diagnosis. <h3>Case Description</h3> At 2 months of age, a male, previously healthy, term baby received routine immunizations to the anterior thigh without immediate adverse effect. Days later he developed small blisters at the prior injection sites, which were pruritic and progressed to large plaques. He was treated unsuccessfully with topical steroid and antifungal creams. At 4 months of age, a skin biopsy was advised which revealed botryomycosis with <i>Staphylococcus aureus</i> as the causative organism. This rare presentation prompted an immunodeficiency work-up, including blood count, immunoglobulins, and dihydrorhodamine testing. Labs revealed neutropenia (620-800 cells/microliter), IgE 1436 IU/mL, and DHR activity was 85% with a subpopulation of reduced activity. Genetic testing revealed a pathogenic mutation of STAT3, diagnostic of an autosomal dominant HIES. Botryomycosis infection resolved on trimethoprim-sulfamethoxazole. <h3>Discussion</h3> Although vaccination can cause benign local skin reactions, botryomycosis is a rare suppurative infection and to our knowledge, there have not been prior reports of botryomycosis diagnosis after vaccination. HIES and botryomycosis are both exceedingly rare and were described together only once. This case underscores that unusual infections with common pathogens are a hallmark of immunodeficiencies.

Genomic Characterisation of Canis Familiaris Papillomavirus Type 24, a Novel Papillomavirus Associated with Extensive Pigmented Plaque Formation in a Pug Dog.

Numerous large dark plaques developed over the ventrum, legs and head of a 9-year-old pug dog over a 4-year-period. Histology confirmed a diagnosis of viral pigmented plaque and a short section of a novel papillomavirus (PV) type was amplified using consensus PCR primers. Taking advantage of the circular nature of PV DNA, 'outward facing' PCR primers allowed amplification of the full sequence. As this is the 24th PV known to infect dogs, the novel PV was designated canine papillomavirus (CPV) type 24. The CPV24 genome contained putative coding regions for 5 early proteins and 2 late ones. The CPV24 open reading frame L1 showed the highest (78.2%) similarity to CPV4 and phylogenetic analysis showed that CPV24 clustered with CPV4 and CPV16 suggesting CPV24 is the third species 2 Chipapillomavirus type identified in dogs. This is the third report of extensive pigmented plaques covering a high proportion of the skin. Both previous cases were caused CPV4 and, considering the high genetic similarity between CPV4 and CP24, infection by these CPV types may predispose to more severe clinical disease. In addition, as plaques caused by CPV16 appear more likely to progress to neoplasia, the detection of a species 2 Chipapillomavirus within a pigmented plaque may indicate the potential for more severe disease.

A 73‐year‐old woman with multiple crusted lesions

A 73-year-old woman was attended for multiple crusted lesions on her head and hands for more than 1 year. These lesions had appeared 1 year ago as red patches with adherent scales without accompanying itch or pain. The patches gradually enlarged and proliferated with thick scales and an ulcer on the left side of her face. The patient suffered from polycythemia vera and had been treated with hydroxyurea (HU), 500 mg daily for 6 years. There was no personal history of local radiotherapy or heavy sun exposure and no family history of malignancy. On examination, several large infiltrated plaques with irregular borders were seen on the eyebrows, cheeks, jaw, nose and hands. The largest one was located on the left cheek (6 × 3 cm2) (Figure 1a,b). A thick scale covered all lesions. In addition, there were smaller red plaques with fine scaling in sun-exposed areas (Figure 1a,b). Lab analyses including blood cell counts and serum chemistry were normal. A skin biopsy from the lesion on her left cheek was done (Figure 1b). Histologic findings of the skin biopsy showed an invasive, moderately differentiated, keratinizing squamous cell carcinoma (SCC). A positron emission tomography scan and ultrasound revealed enlarged lymph nodes on the left side of the neck, but a lymph node biopsy was negative. The lesion on the left cheek was widely excised with complete grafting, and the other lesions were treated with 5% imiquimod cream since the patient declined surgical excision. HU was discontinued and imatinib was started. After 12 months of follow-up, her polycythemia vera was well controlled, no new SCC lesions had developed, and the previous lesions had not progressed. HU is very frequently used as a first-line treatment of polycythemia vera.1-3 HU also has a role in selected skin conditions.4 HU may also play a role in reducing the mortality of coronavirus disease 2019.5 HU selectively acts on the most actively dividing cells such as basal layer keratinocytes. Hence, cutaneous adverse effects have been described, including xerosis, hyperpigmentation and skin atrophy and, less frequently, nonmelanoma skin cancers.3, 6 SCCs associated with HU therapy are seen in patients who used HU for long periods of time. Most patients present multiple SCC lesions.7, 8 The SCCs are usually located in photodistributed areas, which suggests that ultraviolet plays an important adjuvant role in HU-associated SCCs.7-9 Strict photoprotection is thus mandatory in patients on long-term HU therapy. In patients with HU-associated SCCs, HU treatment must be discontinued. Patients should be evaluated basally and then on a regular basis, especially for older patients and those with a propensity to skin cancer.3 As an aggressive and metastatic tumour, the SCCs must be widely excised, and metastases promptly identified and adequately treated.7 So far, no study has compared outcomes in HU-associated SCCs with regular SCCs. Patients on long-term HU therapy must undergo dermatological examination at baseline and regularly thereafter. If a cutaneous malignancy is suspected, a biopsy is mandatory. If malignancy is confirmed, discontinuation of HU must be considered. Ronghui Zhu collected the clinical data and tissue specimens. Shangshang Wang was responsible for the study design and drafted the manuscript. All authors read and approved the final manuscript. This work was supported by grants from the National Natural Science Foundation of China (82003357). The authors declare no conflict of interest. The study was approved by the Institutional Review Board of Huashan Hospital, Shanghai, China, and the patient provided written informed consent. The authors confirm that the data supporting the findings of this case report are available within the article. Raw data that support the findings are available from the corresponding author upon request.

Biomarkers associated with coronary high-risk plaques

Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p < 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively.

First Report of Massive Myocardial Calcifications in a Vervet Monkey (Chlorocebus pygerythrus).

A 13-years-old male vervet monkey that was kept in a primates breeding and research facility at Razi Vaccine and Serum Research Institute, Karaj, Iran (RVSRI) died suddenly. Massively scattered grayish-yellow mottling on both ventricles were the most significant gross necropsy findings. There was a gritty feeling on palpation and sectioning of the yellow areas. Microscopically, the lesions demonstrated scattered degeneration and necrosis of myocardial cells. Inside the affected areas, large calcium deposit plaques were detected using the Von kossa staining method. The development of myocardial calcification in the present case can be attributed to the dystrophic calcification following spontaneous myocardial necrosis or an undetected infection/inflammatory process. Persistent anxiety might trigger spontaneous biventricular necrosis in vervet monkeys. In conclusion, due to similarities between the clinical and histological presentation of the current case with sudden death syndrome associated with myocardial calcification in humans, it was suggested that vervet monkeys might be a relevant animal model for research on the pathophysiological processes of this complication.