Chronic PCSK9 inhibitor therapy leads to sustained improvements in endothelial function, arterial stiffness, and microvascular function.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation. OBJECTIVE: To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect. METHODS: In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO2) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera. RESULTS: Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO2 significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters. CONCLUSIONS: Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.

Pain catastrophizing and employment histories.

BACKGROUND: Studies examining pain catastrophizing and employment have had mixed findings. No study of pain catastrophizing has examined its relationship to lifetime employment status in a general clinical population. AIMS: To examine pain catastrophizing in relationship to lifetime employment functioning in a sample of US primary care patients (rather than injured workers). METHODS: A cross-sectional anonymous self-report survey of consecutive adults in a US internal medicine outpatient clinic. We assessed pain catastrophizing using the Pain Catastrophizing Scale and employment histories using a four-item author-developed measure. RESULTS: There were 239 participants and an initial participation rate of 70%. While pain catastrophizing was not related to the number of different full-time jobs held or the percentage of time employed in adulthood, pain catastrophizing was statistically significantly associated with ever having been paid 'under the table' [F(1,236) = 27.89, P < 0.001] and ever having been fired from a job [F(1,237) = 50.78, P < 0.001], as well as with not getting along with fellow employees [F(1,60) = 7.48, P < 0.01]. CONCLUSIONS: In this clinical sample, pain catastrophizing demonstrated varying relationships with different aspects of lifetime employment, rather than exerting an overall global effect on employment.

Nonenhanced ECG-gated quiescent-interval single-shot MRA (QISS-MRA) of the lower extremities: comparison with contrast-enhanced MRA.

AIM: To evaluate electrocardiogram (ECG)-gated quiescent-interval single-shot magnetic resonance angiography (QISS-MRA) for nonenhanced assessment of peripheral artery occlusive disease (PAOD) using contrast-enhanced MRA (CE-MRA) as the reference standard. MATERIALS AND METHODS: Twenty-seven patients (mean age 66.6 ± 10.8 years) with PAOD were included in the study. QISS-MRA and CE-MRA of the lower extremity were performed using a 1.5 T MR scanner. In each patient, subjective image quality and the degree of stenosis were evaluated on a four-point scale for 15 predefined arterial segments. RESULTS: Twenty-five of the 27 patients were considered for analysis. Subjective image quality of QISS-MRA was significantly lower for the distal aorta, pelvic arteries, and femoral arteries as compared to CE-MRA (p < 0.01), while no significant difference was found for other vascular segments. The degree of stenosis was overestimated with QISS-MRA in 23 of 365 (6.3%) segments and underestimated in two of 365 (0.5%) segments. As compared to CE-MRA, QISS-MRA had a high sensitivity (98.6%), specificity (96%) as well as positive and negative predictive value (88.7 and 99.6%, respectively) for the detection of significant stenosis (≥50%). CONCLUSION: ECG-gated QISS-MRA is a promising imaging technique for reliable assessment of PAOD without the use of contrast material.

The relationship between borderline personality symptoms and body mass index in a consecutive sample of cardiac stress test patients.

Borderline personality disorder (BPD) is characterized by inherent difficulties with self-regulation. While a number of studies have examined the relationship between BPD and body mass index (BMI)/overweight/obesity, findings have been mixed. In this cross-sectional study of a consecutive sample of 238 participants presenting for cardiac stress testing, we investigated the relationship between borderline personality symptoms, according to two self-report measures, and BMI. Compared to participants who were negative on both measures of borderline personality symptoms, participants who were positive on either measure of borderline personality symptoms demonstrated no differences in current BMI or highest BMI in adulthood. These results in a unique study population mirror the findings of other studies in medical and community populations.

Microvascular tissue perfusion after postcatheterization pseudoaneurysm treatment.

BACKGROUND: Femoral pseudoaneurysm (PSA) is a severe complication after endovascular procedures. Ultrasound-guided manual compression (MC) and percutaneous thrombin injection (TI) are frequently used treatments. MC is less effective, TI may cause thromboembolic events. OBJECTIVE: Up to date, there is no data regarding impairment of microvascular tissue perfusion after PSA treatment. METHODS: In this single-center, prospective study 22 patients with PSA were included. We compared macro- and microcirculatory perfusion in the treated and untreated leg at baseline before, after and one day after treatment. Leg perfusion was assessed with ultrasound and ankle-brachial index (ABI). Microcirculatory perfusion of the feet was measured with a near-infrared spectroscopy (NIRS) camera generating StO2-tissue-maps. RESULTS: Successful PSA thrombosis was achieved in 16 (100%) patients in TI group and in 4 (66.7%) patients in MC group. There was no evidence of arterial thrombi on ultrasound and the ABI did not differ between groups. NIRS StO2-tissue-maps of the feet showed no significant difference in both groups concerning the treated (p = 0.121) or the untreated (p = 0.198) leg during follow up. CONCLUSIONS: In this small exploratory study, there was no evidence of micro- and macrovascular tissue perfusion impairment after treatment of postcatheterization femoral pseudoaneurysm with thrombin injection underscoring the safety of this approach.

Eating disorder symptoms and borderline personality symptomatology.

According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.

Splenic infarcts in chronic hepatopathy accompanied by cryoglobulinemia: two case reports.

Splenic infarct is a rare condition often related to haematological, cardiovascular, autoimmune or infectious diseases diagnosed with increasing frequency due to the large use of abdominal imaging techniques. Cryoglobulins are serum proteins that reversibly precipitate at low temperatures, small vessels vasculitis represent their most common clinical manifestation and are often associated with chronic liver disorders or with lymphoproliferative diseases. Here the authors report the cases of two patients, both affected by chronic liver disease associated with cryoglobulinemia, admitted to our unit for an on-going active infectious disease (without signs of endocarditis) who presented multiple splenic infarcts as an unexpected complication. The authors hypotize that in both cases splenic infarct may be related not only to a thrombogenic state or to splenic vasculitis but also to other immuno-mediate mechanism related to cryoglobulins synthesis and clearance.

Antiplatelet effects of aspirin in chronic kidney disease patients.

UNLABELLED: ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. BACKGROUND: The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD. METHODS: We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation. RESULTS: HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006). CONCLUSION: Renal function is correlated with pharmacodynamic response to aspirin. Patients with CKD have an increased risk of impaired antiplatelet effects of aspirin. Larger trials are needed to assess the clinical impact of this finding and investigate the optimal antithrombotic regimen in CKD patients.

Weight loss pressure on a 5 year old wrestler.

The case is reported of a 5 year old boy who was pressured to lose weight in order to wrestle at a lower weight class. Although a minority of athletes engage in unhealthy weight management practices, this is an unusual case because of the age of the athlete and the influential role of a parent.

Validation of High-Resolution Ultrasound Measurements of Intima-Media Thickness of the Radial Artery for the Assessment of Structural Remodeling.

Radial artery (RA) intima-media thickness (IMT) could be used to study short- and long-term structural vascular adaptation following transradial cardiac catheterization. We aimed at assessing the reliability and reproducibility of RA-IMT measurement. Using high-resolution ultrasound, we studied RA-IMT in 17 patients, who underwent transradial catheterization via the right RA 1 to 12 months before. Radial artery intima-media thickness was measured in both arms, with the left RA as control. Repeated measurements were performed by 2 examiners and offline analyses were performed by independent blinded interpreters. Radial artery intima-media thickness was highly reliable with an interclass correlation coefficient (ICC) of 0.911 [0.870-0.939], a high examiner (ICCexaminer 0.910 [0.883-0.931]), and interpreter agreement (ICCinterpreter 0.963 [0.954-0.971]). Intima-media thickness at the radial access site was significantly increased compared with the contralateral RA (0.30 ± 0.056 vs 0.41 ± 0.055 mm, P < .00001). Radial artery intima-media thickness can be measured reliably using high-resolution ultrasound. Initial data suggest that transradial catheterization leads to long-term structural adaption processes.

Prevalence of borderline personality symptoms in two groups of obese subjects.

OBJECTIVE: The purpose of this study was to compare the prevalence of borderline personality symptoms and self-harm behavior in two distinct groups of obese subjects. METHOD: Obese women, 17 from an eating disorders program and 60 from a primary care setting, were administered the borderline personality scale of the Personality Diagnostic Questionnaire--Revised, the Diagnostic Interview for Borderline Patients, and the Self-Harm Inventory. RESULTS: There was a significant between-group difference on all study measures, with subjects in the eating disorders program displaying more psychopathology. CONCLUSIONS: Study group membership appears to have a significant effect on the prevalence of psychopathology in obese women.

Increased health care utilization as a function of participation in trauma research.

OBJECTIVE: This study was designed to compare, in a primary care setting, the health care utilization of women who participated in a trauma research study with the health care utilization of women who did not. METHOD: Health care utilization in the 12 months before and the 12 months after participation in trauma research was determined for both participants (N = 116) and a group of control subjects (N = 100) matched for day of service. RESULTS: Pairwise t test results indicated that for the women who participated in the research, all measures of health care utilization significantly increased in the 12 months after the trauma study; for the control subjects, only the number of ongoing prescriptions significantly increased. Sign tests confirmed that a significantly greater number of research participants demonstrated a positive difference (increase in utilization) for all health care variables, whereas only ongoing prescriptions demonstrated a significant systematic increase among control subjects. CONCLUSIONS: The findings suggest that participation in trauma research may increase subsequent health care utilization.

Affective disorder in the families of women with normal weight bulimia.

The authors determined the lifetime prevalence of affective disorder in the first- and second-degree relatives, excluding children, of 27 bulimic women who had never had anorexia nervosa and 27 women with no history of an eating disorder. Family diagnoses were made blind to the proband's diagnosis. The prevalence of affective disorder was 9% in the relatives of the bulimic probands and 10% in the relatives of the control probands, a nonsignificant difference. These findings are in contrast to reports of an increased prevalence of affective disorder in the relatives of patients with anorexia nervosa.

Borderline personality symptomatology, experience of multiple types of trauma, and health care utilization among women in a primary care setting.

BACKGROUND: This project was designed to explore the relationship between recollected trauma history, borderline personality symptomatology, and health care utilization among women in a primary care setting. METHOD: Women (N = 116) consecutively recruited during routine gynecological appointments were given a set of questionnaires that explored 5 types of trauma (i.e., sexual, physical, and emotional abuse; physical neglect; witnessing violence) as well as borderline personality symptomatology. The preceding 12 months of participants' medical records were blindly reviewed to determine several measures of health care utilization (i.e., number of telephone contacts to the facility, physician visits, ongoing and acute prescriptions, specialist referral). RESULTS: Multiple forms of trauma were related to increased telephone contacts, physician visits, acute prescriptions, and ongoing prescriptions. Borderline personality symptomatology was related to physician visits and ongoing prescriptions. Neither was related to the number of specialist referrals. Total number of types of trauma and borderline personality symptomatology scores were moderately related to each other (r = .36, p < .01). CONCLUSION: With the exception of specialist referrals, the experience of multiple types of trauma and borderline personality symptomatology contribute to higher health care utilization among women in a primary care setting, but not to a substantial degree. The experience of trauma and borderline personality symptomatology appear partially related to each other. This relationship has several implications.

MYCN amplification does not affect survival of neuroblastoma patients treated with autologous bone marrow transplantation.

From an extended series neuroblastoma cases evaluated for MYCN amplification (MNA) at the "G. Gaslini" Hospital 15 (4 with and 11 without NMA) underwent myeloablative therapy and bone marrow transplantation (MAT-ABMT). Such cases ranged in age at diagnosis from 13 months to 7 years and were followed up at least 8 months after MAT-ABMT. MNA was present in 2/10 cases dead for disease, in 0/1 cases alive with disease, and in 2/4 cases presently in complete clinical remission. This preliminary evidence would discourage to consider MNA as a marker capable of predicting the final outcome of patients with metastatic Nb.

Cytogenetic features of neonatal leukemias.

We reviewed a series of 41 neonatal leukemias (NL), including published cases karyotyped by banding techniques, but excluding Down syndrome-associated cases and analyzed distribution of cytogenetic anomalies with respect to other clinical variables and outcome. The most frequent chromosomal changes in this age group involve rearrangements of 11q23, which is correlated with high white blood cell (WBC) count at onset and type of leukemia. A discrete heterogeneity of cytogenetic abnormalities is also evident, however, possibly reflecting other specific pathways in NL development. With respect to prognosis, cytogenetic abnormalities are a strong indicator of poor prognosis.

ins(6;1) in a patient with congenital leukemia.

Q- and C-banded karyotypes of leukemic cells of a patient with congenital acute lymphoblastic leukemia showed the karyotype: 46,XX,ins(6;1)(p21;p13p36). This rearrangement is unusual, and the breakpoints on chromosome 1 are interestingly close to known cellular oncogenes (N-ras, fgr, src-2) and to a putative antioncogene.