Detection of Small Airway Dysfunction in Asthmatic Patients by Spirometry and Impulse Oscillometry System.

BACKGROUND: There is no gold standard in diagnosing SAD. Indicators of SAD are considered: (a) a value <65% of predicted values of two of three measures, FEF25-75, FEF50 e FEF75 (FEF+); (b) a value of FEV3/FEV6 < LLN (FEV3/FEV6+); (c) an IOS value of R5-R20 >0.07 kPa·s·L-1 (R5-R20+). AIM AND OBJECTIVES: The aim of the study was to ascertain, in asthmatic patients, whether spirometry and IOS indicators agree in detecting SAD. We also assessed the relationship between spirometry and IOS indicators and clinical features of asthma. METHODS: We prospectively recruited adult asthmatic patients. Anthropometric and clinical characteristics were recorded. All patients performed spirometry and IOS tests. RESULTS: We enrolled 301 asthmatic patients (179 females; mean age 50 ± 16 years) with normal to moderately severe degree of airway obstruction; 91% were non-smokers, 74% were atopic, 28% had an exacerbation in the previous year, and 18% had a poor asthma control by ACT. SAD was diagnosed in 62% of patients through FEF+, in 40% through FEV3/FEV6+ and in 41% through R5-R20+. κ values were 0.49 between FEF+ and FEV3/FEV6+, 0.20 between FEF+ and R5-R20+, 0.07 between FEV3/FEV6+ and R5-R20+. R5-R20+ but not FEF+ and FEV3/FEV6+ was significantly associated with ACT score (p < 0.05). CONCLUSIONS: Our study shows that in mild to moderately severe asthmatic patients, spirometry and IOS indicators are complementary in diagnosing SAD. Additionally, IOS indicator, but not spirometry ones, was related to asthma control.

Precipitating factors in patients with spontaneous coronary artery dissection: Clinical, laboratoristic and prognostic implications.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) often presents with acute coronary syndrome and underlying pathophysiology involves the interplay between predisposing factors and precipitating stressors, such as emotional and physical triggers. In our study we sought to compare clinical, angiographic and prognostic features in a cohort of patients with SCAD according to the presence and type of precipitating stressors. METHODS: Consecutive patients with angiographic evidence of SCAD were divided into three groups: patients with emotional stressors, patients with physical stressors and those without any stressor. Clinical, laboratoristic and angiographic features were collected for each patient. The incidence of major adverse cardiovascular events, recurrent SCAD and recurrent angina was assessed at follow-up. RESULTS: Among the total population (64 subjects), 41 [64.0%] patients presented with precipitating stressors, including emotional triggers (31 [48.4%] subjects) and physical efforts (10 [15.6%] subjects). As compared with the other groups, patients with emotional triggers were more frequently female (p = 0.009), had a lower prevalence of hypertension (p = 0.039] and dyslipidemia (p = 0.039), were more likely to suffer from chronic stress (p = 0.022) and presented with higher levels of C-reactive protein (p = 0.037) and circulating eosinophils cells (p = 0.012). At a median follow-up of 21 [7; 44] months, patients with emotional stressors experienced higher prevalence of recurrent angina (p = 0.025), as compared to the other groups. CONCLUSIONS: Our study shows that emotional stressors leading to SCAD may identify a SCAD subtype with specific features and a trend towards a worse clinical outcome.

Age-related increases in cardiac excitability, refractoriness and impulse conduction favor arrhythmogenesis in male rats.

The effects of excitability, refractoriness, and impulse conduction have been independently related to enhanced arrhythmias in the aged myocardium in experimental and clinical studies. However, their combined arrhythmic effects in the elderly are not yet completely understood. Hence, the aim of the present work is to relate relevant cardiac electrophysiological parameters to enhanced arrhythmia vulnerability in the in vivo senescent heart. We used multiple-lead epicardial potential mapping in control (9-month-old) and aged (24-month-old) rat hearts. Cardiac excitability and refractoriness were evaluated at numerous epicardial test sites by means of the strength-duration curve and effective refractory period, respectively. During sinus rhythm, durations of electrogram intervals and waves were prolonged in the senescent heart, compared with control, demonstrating a latency in tissue activation and recovery. During ventricular pacing, cardiac excitability, effective refractory period, and dispersion of refractoriness increased in the aged animal. This scenario was accompanied by impairment of impulse propagation. Moreover, both spontaneous and induced arrhythmias were increased in senescent cardiac tissue. Histopathological evaluation of aged heart specimens revealed connective tissue deposition and perinuclear myocytolysis in the atria, while scattered microfoci of interstitial fibrosis were mostly present in the ventricular subendocardium. This work suggests that enhanced arrhythmogenesis in the elderly is a multifactorial process due to the joint increase in excitability and dispersion of refractoriness in association with enhanced conduction inhomogeneity. The knowledge of these electrophysiological changes will possibly contribute to improved prevention of the age-associated increase in cardiac arrhythmias.

Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.

The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.

Looking for optimal antithrombotic strategy after transcatheter left atrial appendage occlusion: a real-world comparison of different antiplatelet regimens.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an effective procedure for the prevention of thromboembolic events in non-valvular atrial fibrillation (AF) patients with contraindications to oral anticoagulation. After the procedure, different antithrombotic regimens have been used, in order to prevent device-related thrombus and trying to minimize bleedings. The search for the optimal antithrombotic strategy is still ongoing. We sought to assess efficacy and safety of different antiplatelet therapy (APT) regimens. METHODS: We enrolled non-randomized consecutive patients who underwent LAAO at the University Hospital of Parma between 2010 and 2021. Three study groups were identified according to post-procedural APT: long (>1, ≤12 months)-dual APT (DAPT), short (≤ 1 month)-DAPT, lifelong single APT (SAPT). The choice of the APT was left to multidisciplinary team evaluation. The incidence of the primary outcome, a composite of any ischemic or hemorrhagic event, was assessed at follow-up. RESULTS: We enrolled a total of 130 patients. Technical success was achieved in 123 (94.6%) patients. After LAAO, 39 [31.7%] patients were discharged on short-DAPT, 35 [28.5%] on long-DAPT and 49 [39.8%] on SAPT. After a median follow-up of 32 months, short-DAPT group had a significantly lower occurrence of the primary outcome (3 [7.7%] vs. 7 [20.0%] in long-DAPT vs. 14 [28.6%] in SAPT, p = 0.049], mainly driven by a lower occurrence of the bleeding endpoint (0 vs. 4 [11.4%] in long-DAPT vs. 9 [18.4%] in SAPT, p = 0.020). Finally, comparison of the Kaplan-Meier curves showed that short-DAPT group had a higher primary endpoint-free survival [p = 0.015] compared to the other groups. CONCLUSION: Post-procedural short-DAPT strategy was associated with better outcomes, mainly driven by reduction of major bleedings.

An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

BACKGROUND: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy. OBJECTIVES: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy. METHOD: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile). RESULTS: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations. CONCLUSION: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder.

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: Q0parma.

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the SERPINA1 gene. Several mutations of SERPINA1 have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare PI*Q0parma variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy.

Sex-Related Differences in Long-COVID-19 Syndrome.

Background: Sex differences have been demonstrated in the acute phase of coronavirus disease 2019 (COVID-19). Women (F) were found to be less prone to develop a severe disease than men (M), but few studies have assessed sex-differences in Long-COVID-19 syndrome. Methods: The aim of this prospective/retrospective study was to characterize the long-term consequences of this infection based on sex. For this purpose, we enrolled 223 patients (89 F and 134 M) who were infected by SARS-CoV-2. In the acute phase of the illness, F reported the following symptoms more frequently than M: weakness, dysgeusia, anosmia, thoracic pain, palpitations, diarrhea, and myalgia-all without significant differences in breathlessness, cough, and sleep disturbance. Results: After a mean follow-up time of 5 months after the acute phase, F were significantly more likely than M to report dyspnea, weakness, thoracic pain, palpitations, and sleep disturbance but not myalgia and cough. At the multivariate logistic regression, women were statistically significantly likely to experience persistent symptoms such as dyspnea, fatigue, chest pain, and palpitations. On the contrary, myalgia, cough, and sleep disturbance were not influenced by sex. Conclusion: We demonstrated that F were more symptomatic than M not only in the acute phase but also at follow-up. Sex was found to be an important determinant of Long-COVID-19 syndrome because it is a significant predictor of persistent symptoms in F, such as dyspnea, fatigue, chest pain, and palpitations. Our results suggest the need for long-term follow-up of these patients from a sex perspective to implement early preventive and personalized therapeutic strategies.

Coronavirus Disease 2019: COSeSco - A Risk Assessment Score to Predict the Risk of Pulmonary Sequelae in COVID-19 Patients.

BACKGROUND: The presence of interstitial pneumonia in coronavirus disease 2019 (COVID-19) patients, as diagnosed through laboratory, functional, and radiological data, provides potential predicting factors of pulmonary sequelae. OBJECTIVES: The objectives were the creation of a risk assessment score for pulmonary sequelae at high-resolution computed tomography (HRCT) through the assessment of laboratory data, lung function, and radiological changes in patients after the onset of COVID-19 interstitial pneumonia and the identification of predictive factors. METHODS: We enrolled 121 subjects hospitalized due to COVID-19 pneumonia in our study. Clinical features, Charlson Comorbidity Index (CCI) score, HRCT score, and blood chemistry data at hospital admission, as well as HRCT score, pulmonary function testing values, exercise capacity by means of a 6-Minute Walk Test (6MWT), and dyspnea perception by the modified Medical Research Council (mMRC) at 4-month follow-up, were all recorded. The variables were elaborated in order to create a predictive model to identify patients at high risk of pulmonary sequelae at HRCT. RESULTS: At the time of follow-up visit, 63% of patients had functional abnormality (diffusion lung capacity and/or total lung capacity <80% of predicted). Age, BMI, CCI, D-dimer, 6MWT, and mMRC were included in the COVID-19 Sequelae Score (COSeSco, ranging 0-15), which was able to individuate COVID-19 patients with radiologic sequelae (HRCT score >10%) at follow-up. The most revelatory COSeSco value that was found to intercept the highest sensitivity (100%) and specificity (77%) was 2. CONCLUSION: The COSeSco - comprising age, BMI, comorbidities, D-dimer, walking distance, and dyspnea perception - makes it possible to identify particularly at-risk COVID-19 patients who are likely to develop pulmonary sequelae assessed by HRCT.

Spontaneous coronary artery dissection: an Italian single centre experience.

AIMS: Spontaneous coronary artery dissection (SCAD) is an emerging cause of acute myocardial infarction (AMI) in young women without a typical cardiovascular risk profile. Knowledge on SCAD is based on observational studies and is still scarce. The aim of this monocentric observational study was to evaluate the predisposing factors, clinical features and prognosis of SCAD patients. METHODS: Between 2013 and 2020, 58 patients with angiographic diagnosis of SCAD were identified in our centre with an overall prevalence of 0.9% among patients admitted for AMI (58 of 6414 patients). RESULTS: The mean age was 54 ±â€Š11 years and the majority were women (n = 50, 86%) with one or fewer cardiovascular risk factors (n = 35, 60%). The prevalence of Fibromuscolar Dysplasia (FMD) was 39% (7 of 18 screened patients). The rate of major adverse cardiovascular and cerebrovascular events (MACCEs) was used to assess the prognosis. Out-of-hospital cardiac arrest because of ventricular fibrillation was observed in four (7%) patients. The majority of patients (n = 51, 88%) were treated conservatively without revascularization. The in-hospital and 30-day clinical course was uneventful in most patients (n = 54, 93%) with two cardiac deaths. During a median follow-up of 12 months, there were no further deaths. The global rate of SCAD recurrence was significant (n = 8, 14%) but predictors have not been identified. CONCLUSION: Although overall survival seems good, SCAD is a potentially malignant, not rare disease, which can present with sudden cardiac death and not uncommon recurrence. Prognostic stratification and optimal management of SCAD patients remain to be defined.

Long-Term Cardiac Sequelae in Patients Referred into a Diagnostic Post-COVID-19 Pathway: The Different Impacts on the Right and Left Ventricles.

Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow-up visit. Clinical features' data about the acute phase along with information about the follow-up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-up of 5 months, echocardiography showed morpho-functional characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and bi-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High-Resolution computed tomography score and hemodynamic Instability (HI), and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies.

Determinants of cardiac structure in frail and sarcopenic elderly adults.

BACKGROUND: Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population. DESIGN: Cross-sectional study. METHODS: We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ≥70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population. RESULTS: All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m2; F = 104 ± 26 g/m2), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of ß blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (ß = 1.51 ± 0.31, p = 0.0005), BSA (ß = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively). CONCLUSIONS: Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population.

Comprehensive Model for Physical and Cognitive Frailty: Current Organization and Unmet Needs.

Aging is characterized by the decline and deterioration of functional cells and results in a wide variety of molecular damages and reduced physical and mental capacity. The knowledge on aging process is important because life expectancy is expected to rise until 2050. Aging cannot be considered a homogeneous process and includes different trajectories characterized by states of fitness, frailty, and disability. Frailty is a dynamic condition put between a normal functional state and disability, with reduced capacity to cope with stressors. This geriatric syndrome affects physical, neuropsychological, and social domains and is driven by emotional and spiritual components. Sarcopenia is considered one of the determinants and the biological substrates of physical frailty. Physical and cognitive frailty are separately approached during daily clinical practice. The concept of motoric cognitive syndrome has partially changed this scenario, opening interesting windows toward future approaches. Thus, the purpose of this manuscript is to provide an excursus on current clinical practice, enforced by aneddoctical cases. The analysis of the current state of the art seems to support the urgent need of comprehensive organizational model incorporating physical and cognitive spheres in the same umbrella.

Interaction of Skeletal and Left Ventricular Mass in Older Adults with Low Muscle Performance.

BACKGROUND: It was recently hypothesized the existence of "cardiac-skeletal muscle axis." However, the relationship between skeletal muscle mass (SMM) and left ventricular mass (LVM) has never been investigated in the specific group of older individuals with low skeletal mass and physical performance. We tested this hypothesis in the SPRINT-T (Sarcopenia and Physical Frailty IN older people: multicomponenT Treatment strategies Trial) population using LVM as independent variable and SMM as dependent variable. METHODS: SMM was assessed by dual-energy X-ray absorptiometry scan and expressed as appendicular lean mass (ALM), and LVM was estimated through echocardiography. Low ALM was defined according to Foundation for the National Institutes of Health Sarcopenia Project criteria, and Short Physical Performance Battery (SPPB) was used to assess physical performance. RESULTS: The population consisted of 100 persons (33 men and 67 women), aged 70 years or older (mean age = 79 ± 5 years) with low ALM and SPPB ranged between 3 and 9, suggestive of physical frailty. Charlson Comorbidity Index median score was 0. Mean value of LVM was 193 ± 67 g, indexed LVM/body surface area (LVM/BSA) was 112 ± 33 g/m2, and cardiac output (CO) was 65 ± 19 L/min. ALM was strongly and positively correlated with LVM (r = 0.54602; P < .0001), LVM/BSA (r = 0.30761; P < .002), CO (r = 0.49621; P < .0001), body mass index (BMI) (r = 0.52461; P < .0001), sex (r = 0.77; P < .001), fat mass (r = 0.38977; P < .0001), and hemoglobin (Hb) (r = 0.26001; P < .01). In the multivariate analysis, LVM (ß = .019 ± .005; P < .0001), CO (ß = .038 ± .016; P = .019), BMI (ß = .286 ± .051; P < .0001), and Hb (ß = .544 ± .175; P = .0025) remained associated to ALM. CONCLUSIONS: In a sample of older persons with low muscle mass and physical performance, LVM was positively and significantly correlated with ALM, independently from blood pressure, physical activity, and other potential confounders. Future studies are needed to address the effect of interventions targeting LVM and SMM.

Hypertrophic cardiomyopathy and nephrogenic diabetes insipidus associated with chronic lithium carbonate use.

Lithium carbonate is an effective mood stabilizer. We treated a patient for hypertrophic cardiomyopathy due to chronic unsupervised lithium carbonate use. We noted: a) a previously normal ECG; b) the absence of any familiarity for sudden cardiac death; c) the associated nephrogenic diabetes insipidus; d) probable exaggerated lithium plasma concentrations, which had not been monitored over the past few years; and e) the unusual traits of the right ventricle. We would like to stress the need for regular cardiologic follow-up in psychiatric patients treated with lithium carbonate, to minimize its potential cardiac untoward consequences.

Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. METHODS: Sixty patients with NVAF underwent LAAO (75.4 ±â€Š9 years); mean CHA2DS2-VASc was 4.4 ±â€Š1.7, mean HAS-BLED 3.2 ±â€Š0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. RESULTS: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ±â€Š1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. CONCLUSION: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding.

Treatment of Delirium in Older Persons: What We Should Not Do!

The presentation of common acute diseases in older age is often referred to as "atypical". Frequently, the symptoms are neither single nor tissue related. In most cases, the onset of symptoms and diseases is the expression of a diminished reserve with a failure of the body system and imbalance of brain function. Delirium is one of the main devastating and prevalent atypical symptoms and could be considered as a geriatric syndrome. It encompasses an array of neuropsychiatric symptoms and represents a disarrangement of the cerebral function in response to one or more stressors. The most recent definition, reported in the DSM-V, depicts delirium as a clear disturbance in attention and awareness. The deficit is to be developed in a relatively short time period (usually hours or days). The attention disorder must be associated with another cognitive impairment in memory, orientation, language, visual-spatial or perception abilities. For the treatment, it is imperative to remove the potential causes of delirium before prescribing drugs. Even a non-pharmacological approach to reducing the precipitating causes should be identified and planned. When we are forced to approach the pharmacological treatment of hyperactive delirium in older persons, we should select highly cost-effective drugs. High attention should be devoted to the correct balance between improvement of psychiatric symptoms and occurrence of side effects. Clinicians should be guided in the correct choice of drugs following cluster symptoms presentation, excluding drugs that could potentially produce complications rather than advantages. In this brief point-of-view, we propose a novel pharmacological flow-chart of treatment in relation to the basic clusters of diseases of an older patient acutely admitted to the hospital and, in particular, we emphasize "What We Should Not Do!", with the intention of avoiding possible side effects of drugs used.

The Relationship Between Widespread Pollution Exposure and Oxidized Products of Nucleic Acids in Seminal Plasma and Urine in Males Attending a Fertility Center.

BACKGROUND: In recent decades, there has been an increase in male infertility, and in many cases, the etiology remains unclear. Several studies relate male hypo-fertility to xenobiotic exposure, even if no data exist about multiple exposure at the environmental level. METHODS: The study involved 86 males with diagnosis of idiopathic male infertility (IMI), and 46 controls with no alteration in sperm characteristics. Seminal plasma (SP) and urine samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify biomarkers of exposure (the main metabolites of benzene, toluene, 1,3-butadiene, 3-monochloropropanediol, styrene, and naphthol) and effect (oxidized products of nucleic acids). RESULTS: Biomarker concentrations were similar in subjects with IMI and controls even if a stronger correlation between biomarkers of exposure and effects were observed in SP. Data show that, both in SP and urine, most metabolites were inter-correlated, indicating a simultaneous co-exposure to the selected substances at the environmental level. Principal component analysis showed in SP the clustering of mercapturic acids indicating a preferential metabolic pathway with Glutathione (GSH) depletion and, consequently, an increase of oxidative stress. This result was also confirmed by multivariable analysis through the development of explanatory models for oxidized products of nucleic acids. CONCLUSIONS: This study highlights how oxidative stress on the male reproductive tract can be associated with a different representation of metabolic pathways making the reproductive tract itself a target organ for different environmental pollutants. Our results demonstrate that SP is a suitable matrix to assess the exposure and evaluate the effects of reproductive toxicants in environmental/occupational medicine. The statistical approach proposed in this work represents a model appropriate to study the relationship between multiple exposure and effect, applicable even to a wider variety of chemicals.

In-situ optical assessment of rat epicardial kinematic parameters reveals frequency-dependent mechanic heterogeneity related to gender.

BACKGROUND: Gender-related cardiac mechanics following the electrical activity has been investigated from basic to clinical research, but results are still controversial. The aim of this work is to study the gender related cardiac mechanics and to focus on its heart rate dependency. METHODS: We employed 12 Sprague Dawley rats (5 males and 7 females) of the same age and, through a novel high resolution artificial vision contactless approach, we evaluated in-situ cardiac kinematic. The hearts were paced on the right atria appendage via cathodal stimuli at rising frequency. RESULTS: Kinematic data obtained at rising pacing rates are different between male and female rat hearts: male tended to maintain the same level of cardiac force, energy and contractility, while female responded with an increment of such parameters at increasing heart rate. Female hearts preserved their pattern of contraction and epicardial torsion (vorticity) at rising pacing rates compared to male. Furthermore, we observed a difference in the mechanical restitution: systolic time vs. diastolic time, as an index of cardiac performance, reached higher value in male compared to female hearts. CONCLUSION: Our innovative technology was capable to evaluate in-situ rat epicardial kinematic at high stimulation frequency, revealing that male preserved kinematic parameters but varying the pattern of contraction/relaxation. On the contrary, female preserved the pattern of contraction/relaxation increasing kinematic parameters.