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Ilaria Cuomo,1,2 Georgios D Kotzalidis,1 Simone de Persis,2 Daria Piacentino,1 Filippo Perrini,2 Emanuela Amici,2 Sergio De Filippis1,2 1Department of Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza School of Medicine and Psychology, Sant’Andrea Hospital, Rome, Italy; 2Department of Neuropsychiatry, Villa von Siebenthal Neuropsychiatric Hospital and Clinic, Genzano di Roma, Rome, Italy Background: To overcome nonadherence in patients with psychosis switch to long-acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus LAI comparisons showed similar antipsychotic responses. Psychoses often overlap with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto focused only on non-comorbid populations. Objective: The objective of this study was to compare two LAIs, administered for 12 months, in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life (QoL) outcomes. Patients and methods: Inpatients were recruited during 2016 and switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients were discharged and followed up for 12 months. Patients were rated at baseline and after 1 year through the Clinical Global Impression scale – severity (CGIs), substance craving intensity was rated through a visual analog scale for substance craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We addressed confounders with backward stepwise logistic regression and three-way analysis of variance. Results: PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM, but AM had a stronger craving for substances at baseline. Both LAIs were associated with significant improvements in all outcomes, with AM displaying stronger effect sizes than PP. The two groups did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year follow-up, AM fared better on all domains. The two groups did not differ in final severity, but PP scored higher than AM in craving at the 1-year endpoint. Limitation: The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias. Conclusion: 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity. AM, compared to PP, improved craving and QoL at the 1-year follow-up. Keywords: psychosis, schizophrenia spectrum and other psychotic disorders, bipolar disorder, long-acting injectable antipsychotic drugs, aripiprazole once-monthly, paliperidone once-monthly

Abstract: In this work we present the findings from a study which aims to produce monodisperse alginate gel droplets within a microfluidic system. To produce alginate drops two aqueous streams, one acidic and one containing alginate and calcium carbonate, merge immediately prior to entering a channel where a continuous flow of sunflower oil breaks the flow of the aqueous phase to form microdroplets. Flow diagrams, which show the relation between the flow rates of the fluids and the flow patterns within the channels, have been produced for different concentrations of alginate, acid and calcium carbonate. It has been found that the production of monodisperse gel drops is governed by two independent factors: the time required for the formation of an alginate structured solution, which depends on the concentrations of the reagents, and the drop formation time, which depends on the flow rates of the fluids. If the drop formation time is shorter than the structuring time regular drop formation is observed, otherwise an alginate structured solution obstructs the channels. The mechanism of drop formation has also been studied and compared with break-up models reported in the literature. [Copyright &y& Elsevier]

Abstract Background B-type natriuretic peptide (BNP) is increased in post-cardiac surgery patients, however the mechanisms underlying BNP release are still unclear. In the current study, we aimed to assess the relationship between postoperative BNP levels and left ventricular filling pressures in post-cardiac surgery patients. Methods We prospectively enrolled 134 consecutive patients referred to our Center 8 ± 5 days after cardiac surgery. BNP was sampled at hospital admission and related to the following echocardiographic parameters: left ventricular (LV) diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV mass, relative wall thickness (RWT), indexed left atrial volume (iLAV), mitral inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral E wave to the Doppler tissue early mitral annulus velocity (E/E'). Results A total of 124 patients had both BNP and echocardiographic data. The BNP values were significantly elevated (mean 353 ± 356 pg/ml), with normal value in only 17 patients (13.7%). Mean LVEF was 59 ± 10% (LVEF ≥50% in 108 pts). There was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p = 0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was directly related to E/E' (p < 0.001), LV mass (p = 0.006) and iLAV (p = 0.026). At multivariable regression analysis, age and E/E' were the only independent predictors of BNP levels. Conclusion In post-cardiac surgery patients with overall preserved LV systolic function, the significant increase in BNP levels is related to E/E', an echocardiographic parameter of elevated LV filling pressures which indicates left atrial pressure as a major determinant in BNP release in this clinical setting.

Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data. [ABSTRACT FROM AUTHOR]

Background: Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients' subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice., Methods: This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations., Results: Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were "markedly or severely ill" showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs., Conclusions: Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction., Trial Registration: NCT06527885 retrospectively registered (01/08/2024)., (© 2024. The Author(s).)

Background: This article analyzes differences in microbiological parameters and periodontal health conditions among three patient groups: those undergoing conventional orthodontic treatment with fixed appliances, patients undergoing orthodontic treatment with clear aligners, and a control group receiving no treatment., Materials and Methods: In this study, 60 patients were enrolled. The microbiological analysis employed a qualitative and semi-quantitative methodology of bacterial morphotype analysis., Results: The analyses revealed a significant difference in favor of clear oral and periodontal health aligners. This could be attributed to better bacterial biofilm removal and reduced mechanical stress on the periodontal ligament, factors facilitated by the ease of clear aligner removal. Significant differences ( p -value < 0.05) were observed for the Full-Mouth Plaque Score, Full-Mouth Bleeding Score, Plaque Index, and periodontal health assessment measurements., Conclusions: Although overall hygiene appears to be improved in patients in the aligners group compared to those treated with conventional orthodontic appliances, there are no statistically significant results regarding plaque composition. Microbiological aspects will be further addressed using more specific techniques in the follow-up of this research.

Background: Partial dopamine D 2 receptor agonists are used for psychotic symptoms in adults with schizophrenia spectrum disorders. Recently, interest surged for partial dopamine D 2 receptor agonists in substance use disorders (SUDs). Since it is believed that SUDs decrease the efficacy of pharmacotherapy of underlying psychiatric disorders, we tested the efficacy of the partial D 2 agonist brexpiprazole in patients with schizophrenia who were either comorbid with a SUD (SUD group) or not comorbid (non-SUD) to assess treatment response and the effect of brexpiprazole on substance craving in SUD., Methods: We included patients with DSM-5/DSM-5-TR schizophrenia (using SCID-5-CV) aged 18-66 years with either comorbid SUD or non-SUD to treat with brexpiprazole 4 mg/day for 6 months during February-October 2022. Patients were assessed with the Clinical Global Impressions-Severity (CGI-S) scale, the 24-item Brief Psychiatric Rating Scale (BPRS), and the Positive And Negative Syndrome Scale (PANSS) at baseline, weekly for the first 2 months and monthly for the next four. Furthermore, we assessed substance craving in SUD with a visual analog scale for craving (VAScrav) at the same timepoints., Results: The total sample was 86 (85 analysable) 18- to 64-year-old (mean 39.32 ± 14.09) patients with schizophrenia [51 men (59.3%) and 35 women (40.7%)], of whom 48 SUD (55.8%) (37 men and 11 women) and 38 non-SUD (44.2%) (14 men and 24 women). No serious or persistent adverse events developed over the study period, but one patient dropped out for subjective akathisia. Results indicated the main effects of time with improvements over the course of the study for CGI-S, BPRS, and PANSS in both SUD and non-SUD groups and the entire sample, and for VAScrav in SUD. Brexpiprazole was associated with similar significant improvements in both groups at the 6 month endpoint compared to baseline., Conclusion: Treatment with brexpiprazole for 6 months improved psychotic symptoms in patients with schizophrenia, independently from whether they belonged to the SUD or the non-SUD group; hence, SUD comorbidity did not confer treatment resistance to brexpiprazole. Furthermore, in the SUD group, we observed reduced substance craving., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lombardozzi, Trovini, Amici, Kotzalidis, Perrini, Giovanetti, Di Giovanni and De Filippis.)

Background: Adverse childhood experiences (ACEs), social-emotional impairments (SEIs), and neurodevelopmental disorders (NDs) are frequent in psychiatric disorders, including substance-use disorders. We aimed to determine the prevalence of ACE, SEI, or ND in individuals with cannabis-use disorder (CUD). We compared individuals with preCUD-onset ACE, SEI, or ND to those without., Methods: We crosssectionally studied 323 inpatients or outpatients with a history of past or current CUD, aged 12-35 years (mean age 22.94 ± 4.79), 64.5% of whom were male. The sample was divided into two groups: the non-premorbid (N = 52) and the premorbid ACE/SEI/ND group (N = 271). Within the premorbid group, further subgroups were based on ACEs, SEI, and NDs. We also analyzed other substance use and psychiatric symptoms/diagnoses based on the non-premorbid-premorbid dichotomy in the CUD sample., Results: Pre-CUD ACE-SEI-ND had higher prevalence of bipolar, schizoaffective, borderline personality, and attention-deficit/hyperactivity disorders, and a history of agitation, hallucinations, and self-injury. The ACE group had higher rates of agitation, depression, delusions, hallucinations, eating disorders, and use of cocaine, amphetamines, and hallucinogens than the SEI or ND. Patients in the premorbid group initiated cannabis use at an earlier age, experienced the first comorbid psychiatric episode earlier, and were hospitalized earlier than those in the non- premorbid ACE-SEI-ND group., Conclusions: PreCUD-onset ACE, SEI, or ND conditions in individuals with CUDare linked to earlier onset of comorbid mental illness. Furthermore, ACEs contribute to significant and potentially severe clinical symptoms, as well as the use of substances other than cannabis.

Background: The Covid 19 pandemic might have impacted response to drug treatment in major depressive episode (MDE). We compared responses to three different antidepressant drugs, i.e., vortioxetine, sertraline, and trazodone, in outpatients with MDE during Major Depressive Disorder (MDD), Bipolar Disorder (BD), or schizophrenia and related psychoses (SSOPDs) during two time periods, i.e., before and after suffering Covid-19-related trauma., Methods: We conducted an observational study on clinically stabilised for at least 6 months outpatients with MDE during the course of MDD (N=58), BD (N=33), or SSOPDs (N=51). Patients, whose baseline assessments of Montgomery-Åsberg Rating Scale (MADRS), Hamilton Anxiety Rating Scale (Ham-A), Brief Psychiatric Rating Scale (BPRS), Visual Analogue Scale for Craving (VAS-crav) and World Health Organization Quality of Life, Brief version (WHOQOL-BREF) were available, were recruited at the time they suffered Covid-19-related traumas. Fifty patients, prior to the pandemic, when they were clinically stable, were treated with 15 mg/die vortioxetine, 44 with 450 mg/die trazodone, and 48 with 150 mg/die sertraline. After experiencing a major Covid-19-related personal trauma, patients showed clinical worsening which required dosage adjustment (20 mg/day vortioxetine; 600 mg/day trazodone, and 200 mg/day sertraline) and, for some of them, hospitalisation. Scores on the MADRS, Ham-A, BPRS, VAS-crav and WHOQOL-BREF were compared drug-wise and genderwise with Student's t test for continuous variables and Χ 2 for categorical variables., Results: The sample consisted of 142 outpatients (age, mean 39.63 ± 16.84; 70 men and 72 women); women were older than men (mean age 43.18 ± 17.61 vs. 35.98 ± 15.30; p=0.01). The two genders did not differ on other variables. For all treatments, worsening symptoms were observed at the time of trauma, followed by slow recovery with treatment readjustment. Trauma-related worsening in patients on vortioxetine was less intense than patients on the other two antidepressants and recovery was faster. All drugs were associated with an improvement in QoL. The vortioxetine group showed a lower hospitalisation rate (24%) than sertraline (35.4%) and trazodone (38.6%), but this was not significant (p=0.27)., Conclusion: All drugs improved symptoms of Covid-19 trauma in patients with MDE, with vortioxetine showing a small advantage. No differences between vortioxetine, sertraline and trazodone were found as concerning the need for hospitalisation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS., Methods: We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity., Results: TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus)., Conclusions: We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years ± 11.82 men, 43.21 years ± 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p  < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 ± 10.09 vs . 27.73 ± 10.35, respectively, p  = 0.001, η2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 ± 4.08, p  < 0.001, η2 = 0.069) and irritable (8.26 ± 4.69, p  < 0.01, η2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (β = -0.55, p  < 0.005) and hyperthymic (β = -0.95, p  < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations . Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18-26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive ( p < 0.001) and negative ( p < 0.001) symptoms and in general psychopathology ( p < 0.001) and decrease in global severity ( p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness., (Copyright © 2020 Giordano, Tomassini, Cuomo, Amici, Perrini, Callovini, Carannante, Kotzalidis and De Filippis.)

Objective: Plasma levels of B-type natriuretic peptide (BNP) are often increased in postcardiac surgery patients. The six-minute walking test (6MWT) is useful to assess functional capacity in postcardiac surgery patients. The aim of this study was to determine whether BNP levels are associated with exercise capacity evaluated by 6MWT in patients after cardiac surgery., Methods: Plasma BNP was measured in 101 consecutive patients referred to our center 8 ± 5 days after cardiac surgery who underwent echocardiography and 6MWT. We considered age, sex, diabetes, renal insufficiency, anemia, chronic obstructive pulmonary disease, hypertension, atrial fibrillation, beta-blocker therapy, left ventricular ejection fraction (LVEF), E/E', indexed left atrial volume (iLAV), type of surgery, and plasma BNP levels as potential predictors of reduced performance at 6MWT evaluated as percentages of the predicted values calculated according to the regression equation obtained in healthy individuals., Results: The mean distance walked at 6MWT was 325 ± 100 m corresponding to 65 ± 20% of the predicted values. This was independent of the LVEF, E/E' or iLAV. Female patients or patients with atrial fibrillation had a reduced performance compared with male patients or patients with sinus rhythm (52 ± 19 vs. 70 ± 19%, P < 0.001; 50 ± 19 vs. 66 ± 19%, P = 0.017, respectively). BNP levels were inversely related to the performance at 6MWT (Pearson's correlation coefficient = -0.25, P = 0.010). At multivariate analysis, female sex (P < 0.001), atrial fibrillation (P = 0.031), and BNP levels (P = 0.040) remained the only independent predictive factors for reduced exercise capacity., Conclusion: The increase in BNP levels in postcardiac surgery patients is associated with reduced exercise capacity.

Background: B-type natriuretic peptide (BNP) is increased in post-cardiac surgery patients, however the mechanisms underlying BNP release are still unclear. In the current study, we aimed to assess the relationship between postoperative BNP levels and left ventricular filling pressures in post-cardiac surgery patients., Methods: We prospectively enrolled 134 consecutive patients referred to our Center 8 +/- 5 days after cardiac surgery. BNP was sampled at hospital admission and related to the following echocardiographic parameters: left ventricular (LV) diastolic volume (DV), LV systolic volume (SV), LV ejection fraction (EF), LV mass, relative wall thickness (RWT), indexed left atrial volume (iLAV), mitral inflow E/A ratio, mitral E wave deceleration time (DT), ratio of the transmitral E wave to the Doppler tissue early mitral annulus velocity (E/E')., Results: A total of 124 patients had both BNP and echocardiographic data. The BNP values were significantly elevated (mean 353 +/- 356 pg/ml), with normal value in only 17 patients (13.7%). Mean LVEF was 59 +/- 10% (LVEF >or=50% in 108 pts). There was no relationship between BNP and LVEF (p = 0.11), LVDV (p = 0.88), LVSV (p = 0.50), E/A (p = 0.77), DT (p = 0.33) or RWT (p = 0.50). In contrast, BNP was directly related to E/E' (p < 0.001), LV mass (p = 0.006) and iLAV (p = 0.026). At multivariable regression analysis, age and E/E' were the only independent predictors of BNP levels., Conclusion: In post-cardiac surgery patients with overall preserved LV systolic function, the significant increase in BNP levels is related to E/E', an echocardiographic parameter of elevated LV filling pressures which indicates left atrial pressure as a major determinant in BNP release in this clinical setting.

Background: Serum C-reactive protein (CRP) is involved in the acute phase reaction after surgery, even though its clinical significance remains a matter of debate. We evaluated CRP levels in cardiac surgery patients without clinical or laboratory signs of infection., Methods: We screened 737 consecutive patients referred to our center 8+/-5 days after cardiac surgery. Patients with fever (>37.2 degrees C), elevated white blood cell count (>11,000/ml), neutrophilia (>70%), or any inflammatory, infective or malignant disease were excluded. CRP levels were measured on admission and at discharge and the values were related to the following variables: age, sex, diabetes mellitus, renal failure, type of surgery, postoperative atrial fibrillation, pericardial or pleural effusion, and length of hospital stay. Follow-up (mean: 23+/-8.5 months) was available for 175 patients (94%)., Results: In the 187 patients enrolled in the study, the CRP values were significantly elevated (median: 4.23 mg/dl, interquartiles range: 2.68-6.64) independent of any variable analyzed. At discharge, CRP levels were significantly reduced compared with values on admission (median: 1.55 mg/dl, interquartiles range: 0.84-2.37, P<0.001). At follow-up, 19 events (10.8%) occurred (two noncardiac deaths, 17 hospital readmissions for cardiac reasons); nonetheless, no correlation was found with CRP values either on admission or at discharge., Conclusion: Early after cardiac surgery, in patients without clinical or laboratory signs of acute infection, CRP levels are significantly elevated, do not correlate with clinical variables, and decrease at discharge. These findings suggest a systemic inflammatory response to surgery-related stress, which carries a favorable prognosis at follow-up.

To evaluate the effect of ammonium persulphate (AP) inhalation on NANC inhibitory (i-NANC) neurotransmitters of guinea pig airways, we exposed eight guinea pigs to AP (1 mg/m3), by aerosol inhalation for 30 minutes daily for three weeks. Control animals inhaled saline aerosol. After the last exposure, the isolated trachea was mounted in an organ bath and electrically stimulated in the presence of hyoscine, piperoxane and propranolol. The i-NANC responses were evaluated as decreases in intraluminal pressure and expressed as area under the curve (AUC, Pa x seconds). The isolated tracheae were treated with a-chymotrypsin, L-NAME, zinc protoporphyrin IX and ODQ, that inhibit the production or action of the single neurotransmitters, like peptides, NO and CO. In the exposed individuals, the NANC relaxations were below 50%, as compared to controls (P < 0.01). NO and CO were the neurotransmitters responsible for all the i-NANC responses, in similar proportions either in exposed individuals or in controls. In conclusion, ammonium persulphate exposure impairs the i-NANC control of airway tone without specifically affecting any neurotransmitter.

Cardiac ultrasound plays a pivotal role in assessing pulmonary artery pressures. Estimation of right atrial pressure can be derived from the dimensions and respiratory variation of the inferior vena cava and Doppler modalities provide an accurate and comprehensive evaluation of right ventricular and pulmonary artery pressures. Peak pulmonary artery pressure can be calculated from continuous wave Doppler sampling of the tricuspid regurgitant jet, while pulsed wave Doppler sampling of the pulmonary regurgitant jet allows evaluation of mean and diastolic pulmonary artery pressures. In patients with tricuspid regurgitation that is either absent or not adequately detectable by Doppler method, Doppler right ventricular outflow tract investigation can be helpful. Recent data indicate that analysis of right ventricular function using myocardial Doppler echocardiography may also provide new insights for the non-invasive estimation of pulmonary artery pressures. In particular, right ventricular isovolumic relaxation time measured by myocardial Doppler echocardiography at the tricuspid annulus may provide an alternative method for estimating pulmonary artery pressure, especially in patients with tricuspid regurgitation not detectable or spectral Doppler not properly interpretable.

Metabolic syndrome is associated with elevated morbidity and mortality for overt coronary artery disease (CAD). In diabetic patients, CAD is often silent. The relation between metabolic syndrome and silent CAD has never been studied. We investigated whether metabolic syndrome is associated with silent CAD in patients with type 2 diabetes mellitus. We evaluated the prevalence of metabolic syndrome in 169 patients with uncomplicated diabetes and angiographically verified silent CAD and in 158 diabetic patients without myocardial ischemia on exercise electrocardiography, 48-hours ambulatory electrocardiography, and stress echocardiography. The groups were comparable for gender, age, glycemic control, and diabetes duration. Metabolic syndrome was defined according to the National Cholesterol Education Program criteria. To estimate insulin resistance in patients treated with diet alone or oral agents (122 patients with CAD and 115 patients without CAD), the Homeostasis Model Insulin-Resistance Assessment (HOMA) was used. The prevalence of metabolic syndrome (59.8% vs 44.3%, p = 0.005) and HOMA (5.4 +/- 2.1 vs 4.9 +/- 2.8, p = 0.044) were significantly higher in those with CAD than in those without CAD. Multiple logistic regression analysis showed that the metabolic syndrome was associated with silent CAD (odds ratio 2.44, 95% confidence interval 1.19 to 5.02, p = 0.015). Among patients on diet alone or oral agents, the HOMA was the strongest predictor of silent CAD (odds ratio 10.16, 95% confidence interval 2.60 to 39.63, p < 0.001). In conclusion, our data have shown an independent association of metabolic syndrome and insulin resistance with silent CAD in patients with type 2 diabetes mellitus. Other studies are needed to establish whether metabolic syndrome and HOMA are reliable markers to identify diabetic patients for additional screening for silent CAD.

Mitral valve prolapse (MVP) is still a clinical challenging problem. In this report, we review the main characteristics of this entity. Epidemiology of MVP, which relies on the diagnostic criteria adopted, and the incidence of complications, both arrhythmic and structural, are influenced by the characteristics of the population studied, which may lead to bias in data interpretation. Even the definition of MVP may differ according to the cardiologist's or cardiac surgeon's point of view. Usually, cardiologists define MVP as the protrusion of all or part of the mitral leaflets into the left atrium, independent of maintenance of coaptation. Therefore, using this definition, mitral regurgitation is considered as a complication rather than a diagnostic criterion. Arrhythmias, either supraventricular or ventricular, are other possible complications, mostly not life-threatening and associated with myxomatous degeneration of the valve. Diagnosis of MVP is based on echocardiography, which provides detailed anatomic and functional evaluation of the affected valve. Leaflet thickness and motion as well as presence and severity of mitral regurgitation can be assessed, with important diagnostic and prognostic implications. Echocardiographic evaluation of the mitral valve requires a systematic approach in order to define the leaflet/scallop involved and the mechanisms of mitral regurgitation. To this aim, three-dimensional reconstruction may add further insights into objective rendering of mitral valve pathology. Finally, surgical timing in mitral regurgitation due to MVP is an evolving issue and the likelihood of surgical repair is a crucial factor in the optimal timing of surgical intervention, especially in asymptomatic patients with severe mitral regurgitation.

Objectives: The aim of this study was to assess the potential value of hand-carried ultrasound (HCU) devices in the diagnosis and follow-up of patients with pleural effusion (PE) after cardiac surgery., Methods: Seventy consecutive patients were evaluated at bedside early after cardiac surgery, in the upright sitting position, using an HCU device on hospital admission and every 3 days until hospital discharge. The posterior chest wall was scanned along the paravertebral, scapular, and posterior axillary lines. For each hemithorax, an effusion index was derived as the sum of the intercostal spaces between the lower and upper limits of the PE along the lines of scanning, divided by 3. A standard chest radiograph was performed in all patients on hospital admission and at hospital discharge, and was qualitatively scored (0, absent; 1, small; 2, large PE). The findings of the HCU device and radiograph were compared using kappa statistics and the Kruskal-Wallis test., Results: A chest ultrasound was feasible in all patients (mean [+/- SD] time, 5 +/- 2 min). Compared with the chest ultrasound, a physical examination showed a sensitivity of 69% and a specificity of 77%. On hospital admission, the HCU device detected a PE in 72 of 140 hemithoraxes. Agreement with the finding of the radiograph was 76% (kappa = 0.52). In 15 hemithoraxes, the HCU device revealed a PE that had not been diagnosed using the radiograph. Conversely, in 18 hemithoraxes a PE that had been diagnosed with a radiograph was not confirmed by the HCU device. The correlation between ultrasound and radiographic scores was statistically significant (p < 0.001). At hospital discharge, a PE was present in 31 of 140 hemithoraxes according to the findings of the HCU device, and in 38 of 140 hemithoraxes according to the findings of the radiograph (agreement, 78%; kappa = 0.44)., Conclusions: In patients early after cardiac surgery, HCU devices allow rapid PE detection and improve the clinical diagnosis. Compared to a radiograph, this method offers the unique advantage of the bedside evaluation of patients without the need for radiation exposure.

The implementation of a digital echocardiography laboratory exists today using the DICOM (Digital Imaging Communication in Medicine) standard to acquire, store and transfer echocardiographic digital images. The components of a laboratory include: 1) digital echocardiography machines with DICOM output, 2) a switched high-speed local area network, 3) a DICOM server with abundant local storage, and 4) a software to manage image and measurement information. The aim of this article was to describe the critical components of a digital echocardiography laboratory, discuss strategies for implementation, and describe some of the pitfalls that we encountered in our own implementation of the digital third level echocardiography laboratory.

Background: The metabolic syndrome is a cluster of cardiovascular risk factors (central obesity, hypertension, dyslipidemia, disturbance in glucose metabolism) associated with insulin-resistance. The cluster of risk factors defining the metabolic syndrome increases cardiovascular risk more than each single component. The aim of the present longitudinal study was to evaluate the relationship between weight loss and changes in insulin-resistance and in the prevalence of the metabolic syndrome 1-year after SAGB implantation., Methods: 51 premenopausal severely obese women (mean age 35.2 +/- 8.8 years, BMI 43.3 +/- 6.9) were enrolled. As a control group, 51 premenopausal non-obese women (BMI < 30) were enrolled. All obese subjects underwent successful implantation of the SAGB via videolaparoscopy. In all subjects insulin-resistance was estimated by HOMA index and metabolic syndrome was defined according to the criteria of the European Group for the Study of Insulin Resistance., Results: HOMA (4.2 +/- 2.0 vs 1.9 +/- 0.8, P < 0.001) and the prevalence of the metabolic syndrome (58.8% vs 7.8%, P < 0.001) were significantly higher in obese than non-obese women. 1 year after SAGB, BMI significantly decreased from 43.3 +/- 6.9 to 34.5 +/- 7.4 (P < 0.001). HOMA index showed a significant dramatic breakdown (4.2 +/- 2.0 vs 2.4 +/- 1.0, P < 0.001). The prevalence of the metabolic syndrome declined significantly (58.8% vs 21.6%, P < 0.001)., Conclusion: Our study shows that in severely obese women, insulin-resistance and the prevalence of the metabolic syndrome significantly decrease 1 year after SAGB. Our findings indicate that SAGB could be a useful tool to reduce the global cardiovascular risk in severely obese people and to improve their long-term prognosis.

Objective: In patients with uncomplicated diabetes, there is low probability of finding significant coronary artery disease (CAD) by noninvasive tests. Therefore, screening for its presence is not justified, and it is important to find reliable predictors of silent CAD to identify patients with uncomplicated diabetes for further screening. The relationship between lipoprotein(a) [Lp(a)], apolipoprotein(a) [apo(a)] polymorphism, and silent CAD has never been studied. We investigated the association of Lp(a) and apo(a) polymorphism with angiographically documented asymptomatic CAD in type 2 diabetic patients without evident complications., Research Design and Methods: A total of 1,323 diabetic patients without any clinical and electrocardiographic evidence of CAD were evaluated. Of 121 patients with highly positive results of exercise electrocardiography (ECG) (n = 30) or positive results on exercise thallium scintigraphy (n = 91), 103 subjects showed angiographically documented CAD (CAD group). Of 1,106 patients with negative results on exercise ECG, 103 subjects without CAD (NO CAD group) were selected and matched by age, gender, and duration of diabetes to patients in the CAD group. In patients in the NO CAD group, results of exercise ECG, 48-h ambulatory ECG, and stress echocardiography were negative for CAD., Results: The CAD group had higher Lp(a) levels (21.7 +/- 17.7 vs. 15.2 +/- 19.0 mg/dl; P = 0.0093) than the NO CAD group, and a percentage of subjects had at least one small apo(a) isoform (68.9 vs. 29.1%; P = 0.0000) higher than the NO CAD group. Logistic regression analysis showed that apo(a) phenotypes (odds ratio [OR] 8.13, 95% CI 3.65-21.23), microalbuminuria (5.38, 2.44-11.88), smoking (2.72, 1.31-5.64), and Lp(a) levels (2.41, 1.15-5.03) were predictors of asymptomatic CAD., Conclusions: Our investigation reports the first evidence of an independent association of Lp(a) and apo(a) polymorphism with asymptomatic CAD. This suggests that Lp(a) levels and apo(a) phenotypes could be used together with other risk factors as markers of asymptomatic CAD in patients with diabetes.

Thermal, mechanical, turbidity, and microscope evidence is provided which strongly suggests molecular interpenetrating network (IPN) formation by mixtures of the seaweed polysaccharides agarose and kappa-carrageenan. Over a range of ionic strength, and potassium content, there is no evidence for synergistic coupling of the networks, and simple phase separation (demixing) can definitely be ruled out. At low ionic strength, where the agarose gels first, differential scanning calorimetry evidence shows some influence of the carrageenan on the agarose ordering enthalpy, particularly at higher polymer concentrations. As the potassium level is increased, however, and the order of gelling is reversed, this effect disappears. Cure behavior for the systems at high ionic strength can be described as a simple summation of the pure component contributions. At low ionic strength, on the other hand, the modulus behavior is more complex, suggesting either a modification, in the mixture, of the kappa-carrageenan gelling parameters or a more complex modulus additivity rule.

The current study focuses on the effects of the molecular weight on the mechanical behavior of agarose gels. The small strain rheology and large strain deformation/failure behavior of three different molecular weight agarose gels have been examined, with the results expressed in term of molar concentration. For small deformation strains, the gelation temperature at low concentrations and the critical concentration for gel formation are strongly affected by the molecular weight. In addition, the elasticity of the network is also very sensitive to this parameter. It has been demonstrated that the experimental gelation cure curves can be superimposed on a universal gelation master curve, independent of the cure time. This would indicate self-similarity of the network at different scales, irrespective of concentration. A relationship between the elastic modulus and the molecular weight has been extracted from these results, where the molecular weight dependence exhibits a power law exponent of 2.42. For large deformation strains, the Poisson ratio has been estimated to be 0.5 for each of the agarose types examined, which indicates that these gels are incompressible. The strain at failure is largely dependent on the molecular weight, and is essentially independent of the biopolymer concentration. This result highlights the fact that the strain at failure is sensitive to the connectivity distances in the gel network. However, the failure stress and Young's modulus of agarose gels show a dependence on both concentration and molecular weight. The observations regarding Young's modulus are in good agreement with those found for small deformation strain rheology for the shear modulus. One of the primary advantages of using the lowest molecular weight agarose is that higher molar concentrations can be reached (more molecules per unit volume). However, the mechanical response of agarose gels is very sensitive to the molecular weight at fixed molar concentration, and if the present results are extrapolated to very low molecular weight, it can be suggested that below a limiting molecular weight a percolating network will not be formed, as suggested by the Cascade model (Carbohydr. Polym. 1994, 23, 247-251). This speculation is based on the influence of the "connectivity" at long distances, which influences the strain at failure (when the strain at failure is zero, the system is not connective).