Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.  Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Quantitative analysis of myocardial blood flow in surgically revascularized and not revascularized myocardial segments. A pilot PET study.

PURPOSE: To prospectively compare changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) in multivessel coronary artery disease (MVCAD) patients undergoing incomplete revascularization (IR) versus complete revascularization (CR) by coronary artery bypass grafting (CABG). METHODS: Seven male patients (age 68 ± 9 years) with MVCAD underwent myocardial perfusion PET/CT with [13N]ammonia before and at least 4 months after CABG. Segmental resting and stress MBF as well as MFR were measured. Resting and during stress left ventricle ejection fraction (LVEF) were also calculated. RESULTS: Three patients (43%) underwent CR and four (57%) IR. Among 119 myocardial segments, 101 (85%) were revascularized, and 18 (15%) were not. After CABG, stress MBF (mL/min/gr) and MFR are significantly increased in all myocardial segments, with a greater increase in the revascularized segments (p = 0.013). In both groups, LVEF significantly decreased during stress at baseline PET (p = 0.04), but not after CABG. CONCLUSION: Stress MBF and MFR significantly improve after CABG in both revascularized and not directly revascularized myocardial segments. IR strategy may be considered in patients with high surgical risk for CR.

Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin.

OBJECTIVE: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS. PATIENTS AND METHODS: One-hundred- seventeen successfully treated first STEMI (age 63.8±12.5 yrs, 70% men) and 64 AS (age 80.3±6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up. RESULTS: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7±2.1 vs. 11.3±1.7, p=ns). GLS cut-off ≤12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS ≤12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (χ2 6.691 vs. 1.364, p=0.010). CONCLUSIONS: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

An enigmatic case of cardiac death in an 18-years old girl.

We report a case of unusual and unexplained cardiac death in an 18-years old female patient with congenital neurosensorial deafness. The fatal event was characterized by an initial syncopal episode, associated with a wide QRS tachycardia (around 110 bpm) but stable hemodynamic conditions. The patient, however, subsequently developed severe hypotension and progressive bradyarrhythmias until asystole and lack of cardiac response to resuscitation maneuvers and ventricular pacing.

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. PATIENTS AND METHODS: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. RESULTS: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. CONCLUSIONS: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

Diagnostic role of echocardiography in patients admitted to the emergency room with suspect no-ST-segment elevation acute myocardial infarction.

OBJECTIVE: We investigated whether echocardiography may help identify, among patients admitted with a suspect of non-ST-segment elevation acute myocardial infarction (NSTEMI), those with athero-thrombotic coronary artery disease (CAD). PATIENTS AND METHODS: We studied consecutive patients admitted with a clinical suspect of first NSTEMI. Echocardiography was assessed within 24 hours from admission. Patients were divided into two groups, according to the results of coronary angiography: 1) patients with obstructive stenosis (≥ 50%) and/or images of thrombosis in one or more coronary arteries (CAD group); 2) patients with no evidence of obstructive coronary arteries (NOCAD group). RESULTS: Of 101 patients enrolled in the study, 53 (52.5%) showed obstructive CAD and 48 (47.5%) NOCAD. At echocardiographic examination, regional wall motion abnormalities were found in 52.8% of patients in the CAD group and 43.7% in the NOCAD group (p=0.43). Left ventricle ejection fraction was 56.4±6.8 vs. 54.7±9.8% (p=0.30) and wall motion score index was 1.16±0.26 vs. 1.21±0.32 (p=0.39) in the two groups, respectively. A multivariable logistic regression independent predictors of obstructive CAD included age, male gender, typical angina, diabetes and hypertension. CONCLUSIONS: Our data showed that, in patients with acute chest pain and increased serum troponin T concentration, routine standard echocardiography does not significantly improve the diagnostic accuracy for the presence of obstructive CAD.

Effectiveness of an educational intervention on seasonal influenza vaccination campaign adherence among healthcare workers of the Palermo University Hospital, Italy.

INTRODUCTION: Healthcare workers are continuously exposed to the risk of being infected by influenza viruses during their work, thus representing a threat especially for fragile patients. Although the Italian Ministry of Health strongly recommends influenza vaccination for all HCWs, coverage levels in Italy are still far from the expected. Several studies report that one of the preferred strategies to improve vaccination coverage among Healthcare Workers is improving vaccination knowledge through specific multidisciplinary courses. To assess the effectiveness of an educational intervention on influenza vaccination coverage among Healthcare Workers a study was conducted at "Paolo Giaccone" University Hospital of Palermo, in the occasion of the 2016/2017 seasonal influenza vaccination campaign. MATERIAL AND METHODS: Educational interventions on influenza infection and vaccination were organized involving personnel of the hospital units in which patients were more fragile. The Healthcare Workers who volunteered attend the course were considered as the intervention group, while two controls for each case, composed by Healthcare Workers not attending it, were randomly selected from the same unit. For both groups, a questionnaire was used to investigate attitude and behaviors toward influenza vaccination, while vaccination coverage data were obtained throughout the Hospital informational data system. RESULTS: Overall, out of the 125 participants, 38 (30.4%) followed the course (intervention group) and 87 (69.6%), not attending the course, represented the control group; later, only 43 Healthcare Workers out of 125 (34.4%) underwent vaccination during the season considered. In particular, after the educational intervention, 42% of the attending Healthcare Workers got vaccinated, while vaccination prevalence in the control group was 31%. The Healthcare Workers who underwent vaccination reported, before the intervention, a higher risk perception for contracting (transmitting) influenza compared to those not vaccinated (p<0.05), while no significant difference in risk perception of transmitting influenza to their patients was reported between the two groups. DISCUSSION: Despite the training provided, and an improvement in vaccination adherence by the Healthcare Workers involved, coverage obtained was lower than recommended to reduce influenza spread in hospital contexts. In conclusion, our data suggest that specific training alone may play a role in the improvement of influenza vaccination adherence, but it should be integrated by a wider range of public health measures, including mandatory vaccination.

Microvascular ischemia in patients with successful percutaneous coronary intervention: effects of ranolazine and isosorbide-5-mononitrate.

OBJECTIVE: About one-third of patients undergoing percutaneous coronary interventions (PCIs) for flow-limiting coronary stenosis continue to develop signs of myocardial ischemia (MI) during exercise stress test [EST], despite successful coronary revascularization. Coronary microvascular dysfunction is a likely major cause of the persistence of EST-induced MI in these patients. PATIENTS AND METHODS: We studied 15 patients (14 men, age 67±5 years) fulfilling the following strict inclusion criteria: (1) recent PCI (<6 months), with drug-eluting stent, of coronary artery stenoses for stable angina, with evidence of full success (no residual stenosis >20% in any vessel); (2) persistence of ST-segment depression induction during EST. After a basal investigation, patients received either ranolazine (375 mg bid) or isosorbide-5-mononitrate (ISMN, 20 mg bid) for 3 weeks in a single-blind, randomized crossover study. Clinical assessment, symptom-limited EST, echocardiographic color-Doppler, with tissue-Doppler examination, and coronary microvascular dilator response to adenosine (CFR-ADO) and cold pressor test (CFR-CPT), assessed by transthoracic echo-Doppler, were obtained at baseline and the end of the 3-week therapy with each drug. RESULTS: Compared to both baseline and ISMN, ranolazine showed a longer time to 1 mm ST-segment depression (404±116 s vs. 317±98 and 322±70 s, respectively; p<0.01). No differences were observed in coronary microvascular function and diastolic left ventricular function between the 2 drugs and compared to baseline. CONCLUSIONS: Our data show that ranolazine, but not ISMN, improved time to ischemia during EST. This effect, however, was independent of any effects on coronary microvascular and diastolic function.

Factors associated with reporting adverse reactions after immunization, study in a sample of university students.

INTRODUCTION: On the day of a workshop (named "Vaccino Day") on vaccinations, organized for the students of the University of Palermo by the ERSU (Regional Office for the Right to University Study), the sample of students were given a questionnaire to fill out. The aim of the survey was to investigate the perception of vaccinations on a sample population made up of university students. STUDY DESIGN: A self-administered paper questionnaire was given to participants of the workshop. The questionnaire is divided into 3 parts: demographic, economic and habits informations have been asked in the first part; in the second part, they had to answer the question: "What term do you associate with vaccination?"; in the third part, they were posed the question: "Have you ever had any adverse reactions after being vaccinated?". Therefore, the percentage response frequencies and the statistically significant Odds-Ratio (aOR) are presented with a corresponding 95% confidence interval (CI). Statistical analysis was performed using the STATA® 14 software. METHODS: A total of 350 students were asked to participate and the response rate was 100%, the 61.43% of the interviewed population was made up of females. Taking into account the dependent variable: "at least a moderate-severe adverse reaction after a vaccination" the statistically significant independent variables associated are "Have fear of side effects" (aOR 7.06, 95% CI 1.73-28.57, p=0.006), "I associate the term "vaccination" to Needles/syringes" (aOR 3.82, 95% CI 1.08-13.48, p=0.037), "I associate the term "vaccination" to Protection" (aOR 3.50, 95% CI 1.02-11.98, p=0.046). DISCUSSION AND CONCLUSIONS: Vaccination is still influenced by emotional factors and lack of campaigns providing adequate information, therefore negative judgement tend to outweigh the real risks and benefits. Considering that the sample was composed of university students, being highly educated and capable of becoming opinion leaders in the future, there is a need to create a more efficient communication protocol that make the student, and then the citizen, better aware of the actual risks associated with vaccinations and their real benefits.

Analysis and Tendencies of Metals and POPs in a Sediment Core from the Alvarado Lagoon System (ALS), Veracruz, Mexico.

This study focused on dating of a sediment core from the Alvarado Lagoon System, Veracruz, Mexico, calculating the sedimentation rate by using 210Pb to determine the tendency towards pollution by polycyclic aromatic hydrocarbons, organochlorides, the metals Cd, Cr, Cu, Hg, Ni, Pb, and V, and organic matter content. The activity of total Pb and supported Pb in the samples was 83.1 and 29.5 Bq kg-1, respectively, whereas the average estimated sedimentation rate was 0.48 ± 0.09 cm per year-1. The organic matter values exhibited linear behavior throughout the historical profile, with values under 2.5%. Metal concentrations followed the order V > Cr > Ni > Cu > Pb > Hg > Cd. Variations found in Cr, Ni, Pb, and V concentrations are basically due to three meteorological phenomena that hit the region: hurricanes Gladys, Hilda, and Janet in September of 1955. V, Ni, and Hg input comes from anthropogenic and lithogenic sources. The presence of individual polycyclic aromatic hydrocarbons showed no ascending accumulation pattern over time, nor did it show any significant statistical correlation to OM. As for the organochlorine pesticides, 63.61% of the total sum of these compounds were from the ciclodienics family. Concentration of p,p'-DDT was observed only in the earliest profile, from 1929.

An update of the Italian Stroke Organization-Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: a personalized medicine approach

Although proof-based medicine has generated much valid evidence for the drawing up of guidelines and recommendations for best clinical practice in symptomatic and asymptomatic carotid stenosis, whether and when it is better to employ endarterectomy or stenting as the intervention of choice still remain matters of debate. Moreover, guidelines have been targeted up to now to the 'representative' patient, as resulting from the statistical analyses of the studies conducted on the safety and efficacy of both interventions as well as on medical therapy alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness Diffusion (SPREAD) group has thus decided to update its statements for an 8th edition. To this end, a multidisciplinary team of authors representing Italian scientific societies in the neurology, neuroradiology, vascular and endovascular surgery, interventional cardiology, and general medicine fields re-examined the literature available on stroke. Analyses and considerations on patient subgroups have allowed to model the risks/benefits of endarterectomy and stenting in the individual. Accordingly, the guideline's original methodology has been revised to follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like approach, integrating it with new considerations on Precision, or Personalized Medicine. Therefore, this guideline offers recommendations on precision medicine for the single patient, and can be followed in addition to the more standard guidelines.

Immunohistochemical evaluation of mismatch repair proteins in colorectal carcinoma: the AIFEG/GIPAD proposal.

Microsatellite instability (MSI) is a hypermutable phenotype that usually arises from either a germline mutation in components of the mismatch repair (MMR) machinery (i.e. hMLH1, MSH2, MSH6 and PMS2) in patients with Lynch syndrome (LS) or somatic hypermethylation of the hMLH1 promoter in sporadic carcinomas. In all colorectal cancers (CRC) is possible to identify the MMR deficiency through protein expression by immunoistochemistry (IHC). Recently, the predictive role of MMR deficiency in reduced chemotherapy benefit and the introduction of universal screening for Lynch syndrome suggest to include MMR testing into routine clinical practice. In this scenario is mandatory to update the minimal requirements for MMR IHC standardization and evaluation. According to international guidelines, these are the GIPAD and AIFEG suggestions for MMR IHC testing.

Correlation between coronary microvascular function and angina status in patients with stable microvascular angina.

BACKGROUND: Classical anti-ischemic drugs are the first-line form of treatment in patients with microvascular angina (MVA), but they often fail to achieve a satisfactory control of angina symptoms. It is unknown whether there is any relation between improvement of angina status and changes in microvascular function induced by classical anti-ischemic drugs in MVA patients. AIM: To assess whether, in MVA patients, the effects of classical anti-ischemic drugs on symptoms and quality of life (QoL) are related to changes in coronary microvascular function. PATIENTS AND METHODS: We studied 51 patients (59±10 years; 15 men) with MVA. Coronary blood flow (CBF) response to adenosine (ADO) and to cold pressor test (CPT), Seattle Angina Questionnaire (SAQ) and EuroQoL scale were assessed at baseline, in pharmacological washout, and after 12 months under anti-ischemic therapy. Patients were divided into 2 groups: (1) Group 1 included patients with no improvement of QoL (EuroQoL score change < 10 points); (2) Group 2 included patients with QoL improvement (increase in EuroQoL score ≥ 10 points). RESULTS: At baseline, the 2 groups were similar in age, gender, cardiovascular risk factors, CBF response to ADO and to CPT, SAQ and EuroQoL scores. At follow-up the 2 groups differed only for beta blockers use (27% vs. 88% in group 1 and 2, respectively; p < 0.001). A significant improvement in SAQ score was observed only in group 2. CBF response to both ADO and CPT showed a similar improvement in the 2 groups. No relation was found between changes in coronary microvascular function and in angina status. CONCLUSIONS: In MVA patients beta-blockers are more effective than other anti-ischemic drugs in improving angina symptoms. The improvement of angina status does not seem to be mediated by changes in coronary microvascular function.

Transcranial magnetic stimulation in the assessment of motor cortex excitability and treatment of drug-resistant major depression.

Major depression is one of the leading causes of disabling condition worldwide and its treatment is often challenging and unsatisfactory, since many patients become refractory to pharmacological therapies. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological investigation mainly used to study the integrity of the primary motor cortex excitability and of the cortico-spinal tract. The development of paired-pulse and repetitive TMS (rTMS) paradigms has allowed investigators to explore the pathophysiology of depressive disorders and other neuropsychiatric diseases linked to brain excitability dysfunctions. Repetitive transcranial magnetic stimulation has also therapeutic and rehabilitative capabilities since it is able to induce changes in the excitability of inhibitory and excitatory neuronal networks that may persist in time. However, the therapeutic effects of rTMS on major depression have been demonstrated by analyzing only the improvement of neuropsychological performance. The aim of this study was to investigate cortical excitability changes on 12 chronically-medicated depressed patients (test group) after rTMS treatment and to correlate neurophysiological findings to neuropsychological outcomes. In detail, we assessed different parameters of cortical excitability before and after active rTMS in the test group, then compared to those of 10 age-matched depressed patients (control group) who underwent sham rTMS. In line with previous studies, at baseline both groups exhibited a significant interhemispheric difference of motor cortex excitability. This neurophysiological imbalance was then reduced in the patients treated with active rTMS, resulting also in a clinical benefit as demonstrated by the improvement in neuropsychological test scores. On the contrary, after sham rTMS, the interhemispheric difference was still evident in the control group. The reported clinical benefits in the test group might be related to the plastic remodeling of synaptic connection induced by rTMS treatment.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

AIMS: Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed. RESULTS: Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function.

BACKGROUND AND AIMS: To assess the effects of bariatric surgery (BS) on peripheral endothelial function and on coronary microvascular dilator function. METHODS AND RESULTS: We studied 50 morbidly obese patients (age 38 ± 9, 13 M) who underwent BS and 20 comparable obese controls (age 41 ± 11, 6 M) without any evidence of cardiovascular disease. Peripheral vascular dilator function was assessed by brachial artery diameter changes in response to post-ischemic forearm hyperaemia (flow-mediated dilation, FMD). Coronary microvascular function was assessed by measuring coronary blood flow (CBF) velocity response to i.v. adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery by transthoracic Doppler echocardiography. The tests were performed at baseline and at 3-month follow-up. At baseline, FMD and CBF response to adenosine and CPT were similar in the 2 groups. Compared to baseline, FMD at follow-up improved significantly in BS patients (5.9 ± 2.7% to 8.8 ± 2.4%, p < 0.01), but not in controls (6.3 ± 3.2% vs. 6.4 ± 3.1%, p = 0.41). Similarly, a significant improvement of CBF response to adenosine (1.63 ± 0.47 to 2.45 ± 0.57, p < 0.01) and to CPT (1.43 ± 0.26 to 2.13 ± 0.55, p < 0.01) was observed in BS patients but not in controls (1.55 ± 0.38 vs. 1.53 ± 0.37, p = 0.85; and 1.37 ± 0.26 vs. 1.34 ± 0.21, p = 0.48, respectively). The favourable vascular effects of BS were similar independently of the presence and changes of other known cardiovascular risk factors and of basal values and changes of serum C-reactive protein levels. CONCLUSIONS: Our data show that, in morbidly obese patients, together with peripheral endothelial function, BS also improves coronary microvascular function. These effects suggest global improvement of vascular function which can contribute significantly to the reduction of cardiovascular risk by BS reported in previous studies.

Endothelial dysfunction as assessed by flow-mediated dilation in patients with cardiac syndrome X: role of inflammation.

BACKGROUND: Endothelial dysfunction, reduced coronary flow reserve and increased markers of inflammation are detectable in cardiac syndrome X (CSX). In this study we investigated the relation between inflammation and systemic endothelial function in CSX patients. METHODS: We studied 42 CSX patients (55 +/- 6 years, 14 men) and 20 healthy subjects (52 +/- 7 years, 9 men). Systemic endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery after 5-minute of forearm cuff inflation. Serum C-reactive protein (CRP) was measured by a high-sensitivity method. RESULTS: FMD was significantly lower in CSX patients compared to controls (4.8 +/- 4.4 vs. 13.7 +/- 4%, p < 0.001), whereas CRP levels were higher in CSX patients than in controls (2.7 +/- 2.4 vs. 0.7 +/- 0.4 mg/L, p = 0.001). In CSX patients FMD showed a significant inverse correlation with CRP levels, even after adjustment for potentially confounding variables (r = -0.34, p = 0.006). CONCLUSION: An impaired FMD is detectable in CSX patients, suggesting a generalized abnormality in vascular function. Subclinical inflammation se is to play a significant role in the impairment of endothelium-dependent vasodilator function of these patients.

Thrombin-inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis.

BACKGROUND: As a regulator of the penultimate step in the coagulation cascade, thrombin represents a principal target of direct and specific anticoagulants. OBJECTIVE: A potent thrombin inhibitor complexed with a colloidal nanoparticle was devised as a first-in-class anticoagulant with prolonged and highly localized therapeutic impact conferred by its multivalent thrombin-absorbing particle surface. METHODS: PPACK (Phe[D]-Pro-Arg-Chloromethylketone) was secured covalently to the surface of perfluorocarbon-core nanoparticle structures. PPACK and PPACK nanoparticle inhibition of thrombin were assessed in vitro via thrombin activity against a chromogenic substrate. In vivo antithrombotic activity of PPACK, heparin, non-functionalized nanoparticles and PPACK nanoparticles was assessed through intravenous (i.v.) administration prior to acute photochemical injury of the common carotid artery. Perfluorocarbon particle retention in extracted carotid arteries from injured mice was assessed via (19) F magnetic resonance spectroscopy (MRS) and imaging (MRI) at 11.7 T. Activated partial thromboplastin time (APTT) measurements determined the systemic effects of the PPACK nanoparticles at various times after injection. RESULTS: An optical assay verified that PPACK nanoparticles exceeded PPACK's intrinsic activity against thrombin. Application of an in vivo acute arterial thrombosis model demonstrated that PPACK nanoparticles outperformed both heparin (P=0.001) and uncomplexed PPACK (P = 0.0006) in inhibiting thrombosis. (19) F MRS confirmed that PPACK nanoparticles specifically bound to sites of acute thrombotic injury. APTT normalized within 20 min of PPACK nanoparticles injection. CONCLUSIONS: PPACK nanoparticles present thrombin-inhibiting surfaces at sites of acutely forming thrombi that continue to manifest local clot inhibition even as systemic effects rapidly diminish and thus represent a new platform for localized control of acute thrombosis.