The risk of cannabis use disorder is mediated by altered brain connectivity: A chronnectome study.

The brain mechanisms underlying the risk of cannabis use disorder (CUD) are poorly understood. Several studies have reported changes in functional connectivity (FC) in CUD, although none have focused on the study of time-varying patterns of FC. To fill this important gap of knowledge, 39 individuals at risk for CUD and 55 controls, stratified by their score on a self-screening questionnaire for cannabis-related problems (CUDIT-R), underwent resting-state functional magnetic resonance imaging. Dynamic functional connectivity (dFNC) was estimated using independent component analysis, sliding-time window correlations, cluster states and meta-state indices of global dynamics and were compared among groups. At-risk individuals stayed longer in a cluster state with higher within and reduced between network dFNC for the subcortical, sensory-motor, visual, cognitive-control and default-mode networks, relative to controls. More globally, at-risk individuals had a greater number of meta-states and transitions between them and a longer state span and total distance between meta-states in the state space. Our findings suggest that the risk of CUD is associated with an increased dynamic fluidity and dynamic range of FC. This may result in altered stability and engagement of the brain networks, which can ultimately translate into altered cortical and subcortical function conveying CUD risk. Identifying these changes in brain function can pave the way for early pharmacological and neurostimulation treatment of CUD, as much as they could facilitate the stratification of high-risk individuals.

Airway Obstruction in Primary Care Patients: Need for Implementing Spirometry Use.

(1) Background: To detect early airway obstruction in an adult primary care setting. (2) Methods: Seventeen general practitioners (GP) were involved. A total of 912 patients consulting their GPs over 40 years were recruited: 583 of them (323M) agreed to perform/undergo all the procedures: respiratory questionnaire, mMRC questionnaire, and spirometry. We identified four subgroups: physician COPD patients; physician asthma patients; asthma-COPD overlap syndrome patients; and no respiratory diagnosis subjects, on the basis of physician diagnosis. For screening purposes, an FEV1/FVC < 70% was considered a marker of airway obstruction (AO). (3) Results: Prevalence rates of COPD, A, and ACOS were 12.5%, 7.8%, and 3.6%, respectively. In the overall sample 16.3% showed airway obstruction: 26% mild, 56% moderate, 17% severe, and 1% very severe. In obstructed subjects, those reporting neither respiratory symptoms nor a physician's respiratory diagnosis were 60% level I; 43% level II; 44% level III; and none level IV. Wheezing (p < 0.001), sputum (p = 0.01), older age (p < 0.0001), and male gender (p = 0.002) were the best predictors of airway obstruction. (4) Conclusions: A high prevalence of AO was found. In AO we found a high prevalence of subjects without respiratory symptoms or respiratory chronic diagnosis. Airway obstruction was predicted by the presence of wheezing, sputum, older age, and male gender.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a survey (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), assessing several symptoms that have been associated with Long-COVID to be administered nationwide to COVID-19 survivors; the survey also included effort perception, measured using the Borg scale. Patients receiving the survey were divided in two groups, with a 2:1 ratio: the first group included patients that received L-Arginine + Vitamin C, whereas the second group received a multivitamin combination (alternative treatment). RESULTS: 1390 patients successfully completed the survey. Following a 30-day treatment in both groups, the survey revealed that patients in the L-Arginine + Vitamin C treatment arm had significantly lower scores compared to patients who had received the multivitamin combination. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p < 0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception.

Relationship between Multimorbidity and Quality of Life in a Primary Care Setting: The Mediating Role of Dyspnea.

Multimorbidity is known to impair Quality of Life (QoL) in patients in a primary setting. Poor QoL is associated with higher dyspnea perception. How multimorbidity and dyspnea perception are related to QoL needs clarification. The aim of the present study is to evaluate the mediating role of dyspnea perception in the relationship between multimorbidity and QoL in adults with and without airflow obstruction in a primary care setting. Seventeen general practitioners participated in the study: a total of 912 adult patients attending the practitioner's surgery for a generic consultation completed a preliminary respiratory screening; 566 of them answered a respiratory questionnaire between January and June 2014, and 259 of the latter (148 M, aged 40-88) agreed to go through all the of procedures including spirometry, the IMCA and QoL (SF-36 through Physical Health "PCS" and Mental Health components) questionnaires, evaluation of comorbidities and the mMRC Dyspnea Scale. For screening purpose, a cut-off of FEV1/FVC < 70% was considered a marker of airflow obstruction (AO). Of the sample, 25% showed airflow obstruction (AO). No significant difference in mMRC score regarding the number of comorbidities and the PCS was found between subjects with and without AO. Multimorbidity and PCS were inversely related in subjects with (p < 0.001) and without AO (p < 0.001); mMRC and PCS were inversely related in subjects with (p = 0.001) and without AO (p < 0.001). A mediation analysis showed that the relation between number of comorbidities and PCS was totally mediated by mMRC in subjects with AO and partially in subjects without AO. We conclude that the effect of multimorbidity on PCS is totally mediated by mMRC only in AO. Detecting and monitoring mMRC in a primary care setting may be a useful indicator for evaluating a patient's global health.

Lung Function Decline in Adult Asthmatics-A 10-Year Follow-Up Retrospective and Prospective Study.

Asthma may have an impact on lung function decline but conflicting results are reported in forced expiratory volume in one second (FEV1) decline. We aimed to describe the changes in FEV1 in lifelong non-smoking adult asthmatic outpatients during a 10-year follow-up comparing years 1-5 (1st period) with years 6-10 (2nd period) to assess factors affecting these changes. A total of 100 outpatients performed spirometry every 3 months during a 10-year survey. FEV1/Ht3 slope values of the 2nd period reduced significantly respect to the 1st period (p < 0.0001). FEV1 slopes of years 1-5 and 6-10 were inversely associated with FEV1 at enrolment (p = 0.02, p = 0.01, respectively). Reversibility and variability FEV1 showed a significant effect on the 1st period slopes (p = 0.01 and p < 0.04, respectively). Frequent exacerbators in the 1st year had steeper FEV1/Ht3 slopes in the 1st period (p = 0.01). The number of subjects using higher doses of ICS was significantly lower at the 10th years respect to the 5th and the 1st year (p < 0.001, p = 0.003, respectively). This study shows that FEV1 decline in treated adult asthmatics non-smokers, over 10-year follow-up, is not constant. In particular, it slows down over time, and is influenced by FEV1 at enrolment, reversibility, variability FEV1 and exacerbation score in the 1st year.

[Periprocedural edoxaban interruption is associated with low bleeding and thromboembolic risk: the Italian data of the EMIT-AF/VTE study]. / Sospensione perioperatoria di edoxaban associata a basso rischio di emorragia e tromboembolia: i dati italiani dello studio EMIT-AF/VTE.

BACKGROUND: So far, the only available data for edoxaban periprocedural management come from the ENGAGE AF-TIMI 48 trial. The recently published EMIT-AF/VTE study showed low periprocedural bleeding and thromboembolic risks of edoxaban in a real-world setting in patients undergoing any diagnostic or therapeutic procedures. The aim of this study was to compare descriptively Italian and European data with regard to patient characteristics and outcomes in the EMIT-AF/VTE study. METHODS: A total of 1155 patients treated with edoxaban for stroke prevention in non-valvular atrial fibrillation and with venous thromboembolism, and undergoing a wide range of diagnostic and therapeutic procedures were enrolled in 326 centers across Europe. Of these patients, 246 were from 43 Italian centers. The periprocedural interruption of edoxaban was at the physician's discretion. All the procedures were classified into minor, low, and high bleeding procedural risk according to the European Heart Rhythm Association (EHRA) definition. The primary outcome was the incidence of major bleeding. Secondary outcomes included thromboembolic events. RESULTS: Patients were older in Italy in comparison with the rest of Europe with a mean age of 74.2 vs 71.3 years. Also, the rate of comorbidities was higher in Italy (e.g. diagnosed cancer and vascular disease) than in Europe. In Italy, there was a higher rate of high bleeding risk procedures than in other European countries (37.8% vs 20.6%) and a more homogeneous distribution of all types of procedures (while in Europe 44.1% were vascular access and transcatheter diagnostic procedures and interventions). In Italy, a higher proportion of patients did not interrupt edoxaban (32.9% vs 29% in Europe). The number of major bleeding events (2 in Italy, 3 in Europe) as well as of thromboembolic events (4 in Italy, 3 in Europe) was overall low. CONCLUSIONS: In the EMIT-AF/VTE study, the number of bleeding and thromboembolic events in patients treated with edoxaban undergoing elective or unplanned procedures was low either in Italy or in the rest of Europe. The safety and efficacy of edoxaban was confirmed in Italy even if patients were older, presented more frequently with cancer, and there was a higher rate of high bleeding risk procedures by EHRA definition.

Safety of Edoxaban 30 mg in Elderly Patients with Severe Renal Impairment.

BACKGROUND AND OBJECTIVE: Patients with atrial fibrillation (AF) and advanced chronic kidney disease (CKD) are at high risk of adverse events and are complicated to manage. There is little evidence on the effects of non-vitamin K oral anticoagulants in patients with severe CKD. Preliminary data in patients taking edoxaban whose creatinine clearance fell below 30 mL/min showed a low risk of stroke and major bleeding. The aim of our study is to test the safety of edoxaban 30 mg/day in patients with severe renal impairment with an estimated glomerular filtration rate (eGFR) of 15-29 mL/min. METHODS: We analyzed retrospective data from 46 patients who had documented AF with severe renal impairment (eGFR between 15 and 29 mL/min). The follow-up, characterized by clinical examination and blood analysis, was performed at 3, 6, and 12 months. The main endpoint was the incidence of major bleedings or clinically relevant non-major (CRNM) bleedings or thromboembolic events. RESULTS: At the time of the data collection, the average follow-up was 9.13 ± 3.0 months. There were no major bleedings, strokes, systemic embolisms, or cardiovascular deaths reported: one non-cardiac death and five minor hemorrhages occurred. No differences related to the severity of CKD were observed in the left ventricular ejection fraction at echocardiography and in the thrombotic and hemorrhagic risk profile. CONCLUSION: In this explorative study analyzing patients with severe CKD treated with edoxaban 30 mg once daily, no major bleeding or thrombotic events were observed. Some minor bleedings were observed. While additional studies are necessary to confirm the results of this exploratory study, edoxaban 30 mg once daily appears to be safe in patients with severe CKD.

[Sudden cardiac death in athletes: is it always not preventable?]. / La morte cardiaca improvvisa negli atleti: è sempre non prevenibile?

Sudden cardiac death (SCD) in athletes is a rare but tragic event particularly considering that in some cases it is preventable. In young athletes with cardiovascular disease the risk of SCD is 2,5 times higher than in non-athletes. In young athletes (<35 years old), the most common causes of SCD are related to pre-existing cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, commotio cordis, some channelopathies and cardiac sarcoidosis. Actually there are two approches to pre-participation athletic screening: the American one based on anamnesis and physical examination and the European one based on anamnesis, physical examination and ECG at rest. However, some disorders responsible for SCD can't be suspected through these exams and it could be useful to implement preparticipation athletic screening.

[Morpho-volumetric assessment of the right ventricle: a comparison between three-dimensional echocardiography and cardiac magnetic resonance]. / Valutazione morfo-funzionale del ventricolo destro: confronto tra ecocardiografia e risonanza magnetica cardiaca.

The morpho-volumetric assessment of the right ventricle (RV) is useful in the diagnosis and prognosis of many congenital and acquired cardiovascular diseases. The complexity of the right ventricular shape does not allow an adequate and satisfactory evaluation of the RV. Two-dimensional (2D) echocardiography is the most used tool for the assessment of RV function, as it is a noninvasive, reproducible and widespread technique, but the geometric assumptions required for measurement of RV volumes reduce its accuracy. At present, cardiac magnetic resonance is the gold standard for the evaluation of RV volumes because it does not need any assumption and is reproducible, though not always available. This imaging tool allows to follow-up patients and to monitor drug therapy. On the other hand, three-dimensional (3D) echocardiography overcomes several limitations of 2D echocardiography, in that it provides an estimation of RV volumes obtained through a real 3D data set, obtaining sections which cannot be technically achieved with 2D echocardiography. It is therefore useful to compare data on RV volumes and function obtained with 3D echocardiography versus cardiac magnetic resonance, mainly considering the lower costs and higher portability and availability of echocardiography.

[Diagnosis, prognosis and treatment of "myocardial bridging": state of the art and unresolved issues]. / Diagnosi, prognosi e terapia del "ponte intramiocardico": stato dell'arte e questioni irrisolte.

The current gold standard for the diagnosis of myocardial bridging is conventional coronary angiography; however, it shows only indirect signs of the disease, due to the systolic compression of the artery caused by the myocardial bridge with narrowing of the lumen and diastolic relaxation. On the other hand, computed tomography coronary angiography, even though exposing to radiation, clearly demonstrates the intramural course, the overlying muscular bands and the surrounding tissues also in asymptomatic patients and in absence of systolic compression. The prognosis of patients with myocardial bridge is usually good, but further studies are needed to evaluate the long-term prognosis of these patients, the adequate diagnostic and preventive approach and to better discern which patients should be candidate to medical, percutaneous or surgical treatment.

Role of bisoprolol in patients with long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a disorder of ventricular repolarization usually treated with ß-blockers, mostly with propanolol and nadolol. The aim of our study was to evaluate the role of bisoprolol in LQTS patients. METHODS: A total of 34 patients were evaluated in an average follow-up time of 93 months: 31 months without treatment, 31 months in treatment with nadolol or propanolol and 31 months in treatment with bisoprolol. The average age of patients at diagnosis was 17.3 years. The enrolled patients were followed through a semiannual electrocardiogram and an annual 24-hour Holter monitoring. All patients underwent genotyping, routine hematologic tests, and an echocardiogram. RESULTS: In 93 months there were 2 major and 12 minor cardiovascular events. Both the major events occurred in absence of ß-blocking therapy. Of the 12 minor cardiovascular events 3 occurred in absence of treatment, 7 during treatment with nadolol or propranolol, and 2 during treatment with bisoprolol. The mean heart rate at 24 h Holter was 87 bpm without treatment, 71 bpm in patients treated with propanolol and nadolol, and 70 bpm in patients treated with bisoprolol. There were not statistically significant differences between the three groups in the mean QTc. CONCLUSIONS: Beta-blocking therapy is the cornerstone of LQTS therapy but actually there is no clear indication about which beta-blocker should be used. In our experience bisoprolol proved to be less harmful and easier to manage than propranolol and nadolol in patients with LQTS, with the same effectiveness in preventing major cardiovascular events.

Drugs to be avoided in patients with long QT syndrome: Focus on the anaesthesiological management.

Long QT syndrome incidence is increasing in general population. A careful pre-, peri- and post-operative management is needed for patients with this syndrome because of the risk of Torsades de Pointes and malignant arrhythmias. The available data regarding prevention of lethal Torsades de Pointes during anesthesia in patients with long QT syndrome is scant and conflicting: only case reports and small case series with different outcomes have been published. Actually, there are no definitive guidelines on pre-, peri- and post-operative anesthetic management of congenital long QT syndrome. Our review focuses on anesthetic recommendations for patients diagnosed with congenital long QT syndrome furnishing some key points for preoperative optimization, intraoperative anesthetic agents and postoperative care plan, which could be the best for patients with c-long QT syndrome who undergo surgery.

An unknown cause of aortic valve stenosis: polycythemia vera.

Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by an abnormal increase in red blood cells. The involvement of the heart during the course of the illness represents a common cause of morbidity and it is linked to an increased thrombogenic risk subsequent to higher blood viscosity. In our study we evaluated by echocardiography a PV patient population. Our study enrolled 44 patients affected by PV. 17 of them were women and 27 were men. Mean patient age was 66.7. The average follow-up period was 5 years and the average duration of the illness was 5.7 years, since the time of diagnosis. All patients were evaluated quarterly by a cardiovascular objective examination and an ultrasound of the heart, with regard to platelet count and hematocrit (Ht) variations during the follow-up period, according to the therapy administered. Patients were treated with hydrossiurea and pipobroman and they underwent an eritrocitoapheresis in emergency conditions in which Ht levels rose too much, in spite of the myelosuppressive therapy. The echocardiographic assessment of the heart structure and function by the B mode technique revealed the presence of a sclerocalcific degeneration of the aortic valve in 58% of patients, involving the aortic root more then the valve. An average trans-aortic flow velocity of 1.92 m/s was detected by Doppler technique; a stenosis was demonstrated in 11 patients (25.5% of the entire population). After diagnosing the presence of a stenosis, we researched a possible cause of it. PV is a systemic disease well-known causing coronary thrombosis in a more or less high percentage of patients according to the record of cases taken into account. In our experience, more then thrombotic disease, found only in 13.4% of patients, we detected a high prevalence and incidence of mild to severe aortic stenosis, found in 25.5% of the sample studied. About all possible causes of stenosis, nowadays this results dependent of Ht values at moment of diagnosis, in the light of these results, it is reasonable to infer that aortic valve stenosis could depend by high haemodynamic stress on valve that is characteristic of polycythemic patients without chemotherapy.

Carotid atherosclerosis and chronic hepatitis C: a prospective study of risk associations.

UNLABELLED: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 ± 0.21 versus 0.90 ± 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P = 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P = 0.03), were independently linked to the presence of carotid plaques. In patients ≤55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis (P = 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P = 0.51). CONCLUSION: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients.

Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction.

Heat shock proteins (Hsps) are produced in response to various stressors, including ischemia-reperfusion, and they can exit cells and reach the blood. In this pilot study, we determined serum levels of Hsp60 and heme-oxygenase-1 (HO-1; also named Hsp32) in subjects with acute myocardial infarction (AMI) to assess their clinical significance and potential prognostic value. We also performed a bioinformatics analysis of the 2 molecules in search of structural clues on the mechanism of their release from cells. We studied 40 patients consecutively admitted for AMI (male:female patient ratio=20:20, mean age: 64 ± 13 years) and 40 matched controls. A blood sample was drawn for biochemical analyses within 24 h of symptoms onset, and Hsp60 and HO-1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). All patients were followed up for 6 months to register adverse post-AMI cardiovascular events. A multivariate analysis demonstrated that elevated Hsp60 (P=0.0361), creatine phosphokinase-muscle brain (CK-MB) (P=0.0446), and troponin (P=0.0490) were predictive of post-AMI adverse events. In contrast, increased HO-1 showed a significant association with less severity of coronary artery diseases (P=0.0223). These findings suggest that Hsp60 and HO-1 play distinct roles in the pathogenesis of AMI and subsequent AMI-related pathology. The possibility that these proteins differ in their roles and mechanisms of action in AMI and post-AMI pathology was supported also by the bioinformatics estimates of probability of their localization in various subcellular compartments. The results clear the way for subsequent investigation on the pathogenetic role and clinical significance of Hsp60 and HO-1 in AMI.

Atherosclerosis, degenerative aortic stenosis and statins.

Aortic stenosis is the most common valvular heart disease among adult subjects in western countries The current treatment for aortic stenosis is aortic valve replacement. The possibility of a medical treatment that can slow the progression of aortic stenosis is very fascinating and statins have been tested to reduce the progression of degenerative aortic stenosis (DAS). The rationale for statin treatment in DAS has a deep pathophysiological substrate, in fact inflammation and lipid infiltration constitute the same histopathological pattern of both aortic stenosis and atherosclerosis and these two conditions have the same risk factors. Whether retrospective studies have shown some efficacy of statins in halting the progression of DAS, prospective trials have shown controversial results. A recently published large and randomized controlled trial SEAS found that statins have no significant effect on the progression of aortic stenosis, the ASTRONOMER, recently confirmed this data. The most plausible hypothesis is that coronary artery disease and DAS, have a common pathogenetic background and a distinct evolution due to different factors (mechanical stress, genetic factors, interaction between inflammatory cells and calcification mediators). Thus, treatment with statins is not recommended in patients with valvular aortic stenosis and without conventional indications to lipid-lowering treatment.

Novo, S. et al. Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule Predestinated to Replace Arbs and Ace-Inhibitors? Pharmaceuticals 2009, 2, 118-124.

In the published version "Paladini et al. reported that aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg [25]". Paladini et al. should be Palatini et al., and the cited reference number should be [10], not [25].. In the sentence, "Early data suggest a role for aliskiren in preventing end-organ damage but, considering the ONTARGET results with an ACE-I-ARB combination, outcome studies are needed before the use of aliskiren can be recommended in combination with other RAS inhibitors [18-30]" one more citation number was added [5], so the revised sentence is "Early data suggest a role for aliskiren in preventing end-organ damage but, considering the ONTARGET results with an ACE-I-ARB combination, outcome studies are needed before the use of aliskiren can be recommended in combination with other RAS inhibitors [5,18-30]". [...].