Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

Objective

Several studies have demonstrated that carotid plaque rupture and thrombosis represent the most important factors correlated with the onset of acute cerebrovascular symptoms. Nevertheless, ruptured thrombotic plaques have been described also in asymptomatic patients. What still needs to be clarified is why a plaque rupture leads either to an acute ischemic syndrome or, in a minor group of patients, remains asymptomatic. The purpose of this study was to systematically compare the histologic features of thrombotic plaques both in asymptomatic and symptomatic patients in order to identify specific findings that could explain the peculiar clinical behavior that characterizes each of the clinical settings.

Methods

A total of 157 thrombotic plaques from 60 asymptomatic patients and 97 with major stroke who consecutively underwent CEA were serially sectioned and studied by histology.

Results

A minute cap disruption very frequently characterizes thrombotic plaques of asymptomatic patients and it was always smaller than large ulcers observed in thrombotic symptomatic plaques (651 ± 687 μm vs. 4150 ± 3526, p = 0.001). In asymptomatics this typical feature was associated with fewer inflammatory cells (20.1 ± 8.8 vs. 33.9 ± 26.1 cells × hpf, p = 0.001), smaller lipidic–necrotic core (33.9% ± 2.9% vs. 42.0% ± 2.4%; p = 0.04) and larger calcification (16.2 ± 12.8% vs. 8.1 ± 12.2%, p = 0.02). Symptomatic patients with thrombotic plaques showed higher incidence of metabolic syndrome (p = 0.002) and moderate-high Framingham risk scores (p = 0.001) comparing to asymptomatic individuals.

Conclusion

The transformation from a stable to a vulnerable plaque is a gradual process in the natural history of the disease and plaque rupture is an event not necessarily occurring at a late phase but also at earlier one. In this case, the rupture will be most likely smaller and clinically asymptomatic.     

A pathobiologic link between risk factors profile and morphological markers of carotid instability

ObjectiveAlthough cardiovascular risk factors have been strongly linked to carotid intimal-media thickness, their association with plaque progression towards instability is poorly understood.We evaluated a large database of endarterectomy specimens removed from symptomatic and asymptomatic patients to determine the correlation between major cardiovascular risk factors and carotid plaque morphology.MethodsIncidence of thrombotic, vulnerable and stable plaques together with the degree of plaque inflammatory infiltration was evaluated in 457 carotid atherosclerotic lesions. Clinical records were reviewed in all cases for risk factors profile.ResultsThrombotic plaques were more frequently observed in patients affected by stroke (66.9%) as compared to TIA (36.1%) and asymptomatic patients (26.8%, p < 0.001). Out of 457 carotid plaques removed during carotid endarterectomy, 181 (39.6%) were represented by thrombotic plaques, 72 (15.8%) by vulnerable plaques (thin cap fibroateroma) and 204 (44.6%) by stable plaques. At the multivariate analysis, a strong association was observed between hypertension, low HDL-cholesterol (HDL-C) and ratio of total to HDL-C >5 with vulnerable and thrombotic carotid plaques. Hypertension (p = 0.001), hypercholesterolemia (p = 0.05) and low HDL-C (p = 0.001) significantly also correlated with the presence of high inflammatory infiltrate of the plaque. When multivariate analysis was restricted to asymptomatic patients, hypertension (p = 0.009, OR 2.29), low HDL-cholesterol (p = 0.01 OR 2.21) and the ratio of total to HDL-C >5 (p = 0.03, OR 2.07) were confirmed to be the risk factors most significantly associated to unstable plaques. The relative risk to carry an unstable plaque for asymptomatic patients with high Framingham Risk Score as compared with those with low risk score was 2.06 (95% C.I., 1.26–3.36).ConclusionsThe present histopathological study identifies risk factors predictive of increased risk of carotid plaque rupture and thrombosis. Asymptomatic patients with high risk factors profile may constitute a specific target to reduce the likelihood of cerebrovascular accidents even in the presence of non-flow-limiting plaque.     

Feasibility and Clinical Efficacy of a Multidisciplinary Home-Telehealth Program to Prevent Falls in Older Adults: A Randomized Controlled Trial

Objectives

The aim of this study was to determine the feasibility and efficacy of a 6-month tele-rehabilitation home-based program, designed to prevent falls in older adults with 1 or more chronic diseases (cardiac, respiratory, neuromuscular or neurologic) returning home after in-hospital rehabilitation for their chronic condition. Patients were eligible for selection if they had experienced a fall during the previous year or were at high risk of falling.

Gender and 5-years course of psychosis patients: focus on clinical and social variables

Most studies on gender and psychosis have focused on gender differences at illness onset or on the long-term outcome, whereas little is known about the impact of gender on the first years after...     

Clinical manifestations of coronary aneurysms in the adult as possible sequelae of Kawasaki disease during infancy

Coronary artery aneurysms are rare findings usually diagnosed incidentally at necropsy or at angiography in patients with symptoms of myocardial ischaemia. Even if atherosclerosis is a common cause of coronary aneurysms in the adult, other acquired diseases with inflammatory pathogenesis are associated with coronary artery aneurysms. We present three cases of patients with low probability of coronary artery atherosclerotic disease, due to their age, risk factors profile and history, complaining of chest pain suggestive of myocardial ischaemia and angiographic documentation of one or more coronary aneurysms. In all cases, although no patient had had a previous diagnosis of Kawasaki disease (KD), an unexplained febrile syndrome had occurred in childhood, which is compatible with misdiagnosed episode of KD causing the aneurysmatic lesions. The present reports highlight the potential clinical relevance of previously misdiagnosed KD in patients with ischaemic chest pain, low probability of atherosclerosis and coronary aneurysms.     

Pattern of experienced and anticipated discrimination among people with depression in Nigeria: a cross-sectional study

Purpose

Stigma is commonly encountered by individuals with mental illness and leads to discrimination. These phenomena restrict access to and use of mental health care services. This study evaluated the impact of stigma and discrimination among individuals with major depression in Nigeria.

Methods

A cross-sectional study was conducted across four tertiary psychiatric facilities located in different regions of Nigeria. Consenting adults attending the psychiatric units in the participating sites with a diagnosis of a major depressive disorder and having an episode within the past 12 months were recruited. Interviews were conducted using a socio-demographic questionnaire, the Discrimination and Stigma Scale, the Internalized Stigma of Mental Illness Scale, the Boston University Self Empowerment Scale, and the Rosenberg Self Esteem Scale.

Results

One hundred and three interviews were completed. The mean age of the participants was 35.5 years. The most frequent item for experienced discrimination was being unfairly treated in dating or intimate relationships (13.6 %), while concealment of mental illness was the most common for anticipated discrimination (51.5 %). Younger people (age less than 40 years) with a higher level of education appear to be at high risk for experienced discrimination.

Conclusions

Important suggestions may be derived for clinicians, caregivers, and policy makers to appreciate the role of stigma in the burden, treatment, and rehabilitation of individuals with depression, especially for younger people with higher level of education.     

A Dominant STIM1 Mutation Causes Stormorken Syndrome

Stormorken syndrome is a rare autosomal‐dominant disease with mild bleeding tendency, thrombocytopathy, thrombocytopenia, mild anemia, asplenia, tubular aggregate myopathy, miosis, headache, and ichthyosis. A heterozygous missense mutation in STIM1 exon 7 (c.910C>T; p.Arg304Trp) (NM_003156.3) was found to segregate with the disease in six Stormorken syndrome patients in four families. Upon sensing Ca²⁺ depletion in the endoplasmic reticulum lumen, STIM1 undergoes a conformational change enabling it to interact with and open ORAI1, a Ca²⁺ release‐activated Ca²⁺ channel located in the plasma membrane. The STIM1 mutation found in Stormorken syndrome patients is located in the coiled‐coil 1 domain, which might play a role in keeping STIM1 inactive. In agreement with a possible gain‐of‐function mutation in STIM1, blood platelets from patients were in a preactivated state with high exposure of aminophospholipids on the outer surface of the plasma membrane. Resting Ca²⁺ levels were elevated in platelets from the patients compared with controls, and store‐operated Ca²⁺ entry was markedly attenuated, further supporting constitutive activity of STIM1 and ORAI1. Thus, our data are compatible with a near‐maximal activation of STIM1 in Stormorken syndrome patients. We conclude that the heterozygous mutation c.910C>T causes the complex phenotype that defines this syndrome.     

Tetrachloroethane, pentachloroethane, and hexachloroethane: genetic and biochemical studies

Tetrachloroethane (TTCE), pentachloroethane (PCE), and hexachloroethane (HCE) were tested in diploid strain (D7) of the yeast Saccharomyces cerevisiae in suspension test with and without mammalian metabolic activation (S9). TTCE, PCE, and HCE gave positive results on cells harvested from logarithmic growth phase; only PCE induced a significant increase (P less than or equal to .01) of mitotic gene conversion and point reverse mutation on cells from stationary growth phase with metabolic activation (S9). The in vivo effects on cytochrome P450 content (cyt. P450), pentoxyresorufin O-dealkylase (P450-like, class IIB, PROD), and ethoxy-resorufin O-deethylase (P448-like, class IA, EROD) activities were examined in hepatic microsomes from mice 24 h after acute intoxication. All the halogenated hydrocarbons displayed a marked toxic effect as shown by the significant decrease in cyt. P450 levels (maximum of 76% decrease, with TTCE 753.2 mg/kg) and EROD (maximum of 69% decrease, with PCE 925.4 mg/kg), and to a lesser extent in PROD (maximum of 52.4% decrease, with HCE 3150 mg/kg). Although a general decrease of P450 functions was observed, the toxic effects of TTCE and PCE seem to be preferentially related to P448 forms.