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.

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.

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.

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.

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.

Left ventricular geometry correlates with early repolarization pattern in adolescent athletes.

Some forms of early ECG repolarization QRS pattern (ERp) with J-point elevation of 0.1 mV in two contiguous inferior and/or lateral leads with or without ST-elevation are potentially associated with a higher arrhythmic risk in adults. We assessed the prevalence of ERp among non-professional adolescent athletes and correlated it with age, sex, ethnicity, and structural and electric cardiac parameters. We retrospectively analyzed 414 ECGs obtained from young athletes referred to our center from 2006 to 2017. We found ERp in 22% of cases. In the ERp group, we found a greater percentage of black athletes, a higher systolic blood pressure, and lower heart rate (HR) compared with the group without ERp. This pattern was less frequent in female athletes. In athletes with ERp, the occurrence of ventricular ectopic beats was less frequent and QRS-duration was shorter. They also exhibited greater (a) ECG-based left ventricular hypertrophy (LVH), (b) left ventricular mass, and (c) relative wall thickness (RWT), suggesting a tendency to concentric geometry. At logistic regression analysis, we found that HR (OR 0.98 [0.96-0.99] P = .013), QRS-duration (OR 0.96 [0.94-0.99], P = .003), LVH (OR 1.09 [1.05-1.12], P < .001), and RWT (OR 1.08 [1.01-1.16] P = .032) were significant predictors of ERp incidence. ERp is quite common in adolescent athletes and correlates with concentric LV remodeling. Specific clinical and ECG-findings related to training such as lower HR, LVH, and QRS-duration are also predictors of ERp. In adolescent non-professional athletes, ERp is a benign finding associated with some structural and electric cardiac modifications induced by training.

[Laboratory animal allergy.] / Allergia da animali da laboratorio.

SUMMARY: Laboratory animal allergy (LAA) is caused by an immunological hypersensitivity reaction to highmolecular- weight antigens that are present in laboratory animals' urine, dander and saliva. All laboratory animal facility personnel who regularly come in contact with laboratory animals, such as technicians, researchers, cleaning staff, veterinarians and even administrative staff, are at risk of developing LAA. Generally, most epidemiological studies indicate a LAA prevalence ranging from 6% to 44% and an incidence ranging from 9% to 30%. Prevalence and incidence data vary widely because the diagnosis is not uniformly defined: some diagnoses are made solely on the basis of symptoms, whereas others also require a positive skin test or confirmation of the presence of laboratory animal allergen-specific IgE antibodies.

Idiopathic pulmonary fibrosis and occupational risk factors.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin that rapidly leads to death. However, the rate of disease progression varies from one individual to another and is still difficult to predict. The prognosis of IPF is poor, with a median survival of three to five years after diagnosis, without curative therapies other than lung transplantation. The factors leading to disease onset and progression are not yet completely known. The current disease paradigm is that sustained alveolar epithelial micro-injury caused by environmental triggers (e.g., cigarette smoke, microaspiration of gastric content, particulate dust, viral infections or lung microbial composition) leads to alveolar damage resulting in fibrosis in genetically susceptible individuals. Numerous epidemiological studies and case reports have shown that occupational factors contribute to the risk of developing IPF. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of occupational factors in the pathogenesis and prognosis of the disease. Prompt identification and elimination of occult exposure may represent a novel treatment approach in patients with IPF.

ALLiance for sEcondary PREvention after an acute coronary syndrome. The ALLEPRE trial: A multicenter fully nurse-coordinated intensive intervention program.

The main objective of cardiovascular disease prevention is to reduce morbidity and mortality by promoting a healthy lifestyle, reducing risk factors, and improving adherence to medications. Secondary prevention after an acute coronary syndrome has proved to be effective in reducing new cardiovascular events, but its limited use in everyday clinical practice suggests that there is considerable room for improvement. The short-term results of evidence-based studies of nurse-coordinated secondary prevention programs have been positive, but there is a lack of long-term outcome data. The Alliance for the Secondary Prevention of Cardiovascular Disease in the Emilia-Romagna region (ALLEPRE) is a multicenter, randomized, controlled trial designed to compare the effects of a structured nurse-coordinated intensive intervention on long-term outcomes and risk profiles after an acute coronary syndrome with those of the standard of care. All of the patients randomized to the intervention group take part in 9 one-to-one sessions with an experienced nurse from the participating centers with the aim at promoting healthy lifestyles, reducing risk factors, and increasing adherence to medication over a mean period of 5 years. The primary clinical end point is the reduction in the risk of the 5-year occurrence of major adverse events (a composite of cardiovascular mortality, nonfatal reinfarction, and nonfatal stroke). The primary surrogate end point is the achievement of prespecified targets relating to classical risk factors, lifestyle modifications, and adherence to pharmacological therapy after 2 years of follow-up. Coronary heart disease is a chronic degenerative disease, and patients who recover from an acute coronary syndrome (ACS) are at high risk of developing recurrent events.1 Although secondary prevention measures have proved to be effective and are strongly recommended by all of the international guidelines,2., 3. the 4 EUROASPIRE surveys4., 5., 6., 7., 8. showed that there was still a high prevalence of conventional risk factors, that secondary prevention measures were inadequately implemented, and that their main goals were often not reached. In addition, there were considerable discrepancy in secondary prevention practices between centers and countries, and a widespread underuse of cardiac prevention and rehabilitation programs despite their demonstrated effectiveness in reducing cardiovascular risk over time.9., 10. Over the last 10 years, nurses have been increasingly involved in successful cardiovascular risk management,11., 12., 13. but although this has improved levels of cardiovascular risk, no clear reduction in hard end points such as major cardiovascular adverse events and mortality has been demonstrated.10 The aim of the ALLEPRE trial is to evaluate the benefit of a homogeneous, structured, secondary prevention intervention program, fully coordinated by nurses from in- and outpatient clinics, in terms of cardiovascular risk profiles and major clinical events in ACS patients living in the large Emilia-Romagna region of Italy.

Resolution of late-onset heart and liver failures after reversion of jejuno-ileal bypass: a case report.

OBJECTIVES: Jejuno-ileal bypass (JIB) was a kind of bariatric surgery performed from 1960s to 1980s, able to induce sustainable weight loss by creating a surgical short bowel syndrome. MATERIALS AND METHODS: We report a case of an octogenarian woman who underwent in the early eighties this kind of surgery with consequent 40 kg weight loss. After 27 years, she first developed a reversible metabolic cardiomyopathy that began with signs and symptoms of heart failure. Thereafter, she was diagnosed with severe intractable liver insufficiency. RESULTS: Despite her old age, the patient underwent reversal of JIB with consequent early improvement of hepatic function. CONCLUSIONS: This case demonstrate that in case of long-term and life-threatening complications, it is possible to successfully reverse JIB surgery after upto 30 years. The hypothesis on pathophysiology of heart and liver insufficiency are discussed.

Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans.

Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 µg·kg-1·min-1 NG-nitro-l-arginine methyl ester (l-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2αV; an oxidative stress marker) were measured. With PL + l -NAME, the following changes were observed: +6% MAP (P < 0.005 vs. baseline), -10% GFR, -20% RBF, -49% UNaV (P < 0.001), and +120% U8-iso-PGF2αV (P < 0.01). In contrast, MAP did not increase during LOS + l-NAME or MANI + l-NAME (P > 0.05 vs. baseline), whereas renal changes were the same during LOS + l-NAME vs. PL + l-NAME (ANOVA, P > 0.05). However, during MANI + l-NAME, changes vs. baseline in GFR (-6%), RBF (-12%), and UNaV (-34%) were blunted vs. PL + l-NAME and LOS + l-NAME (P < 0.005), and the rise in U8-iso-PGF2αV was almost abolished (+37%, P > 0.05 vs. baseline; P < 0.01 vs. PL + l-NAME or LOS + l-NAME). We conclude that, since MANI blunted l-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2αV was essentially prevented during MANI + l-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability.

Nitric oxide-angiotensin II interactions and renal hemodynamic function in patients with uncomplicated type 1 diabetes.

The objective is to elucidate the effect of nitric oxide (NO)-renin-angiotensin system (RAS) interactions on renal hemodynamic function in uncomplicated, type 1 diabetes mellitus (DM). In 14 salt-replete, male healthy volunteers (C) and 9 male DM patients on euglycemia, glomerular filtration rate (GFR), renal blood flow (RBF), filtration fraction (FF), and sodium excretion (UNaV) were measured at baseline and during a 90-min infusion of 3.0 µg·kg⁻¹·min⁻¹ NG-nitro-L-arginine-methyl-ester (L-NAME) after 3 days of pretreatment with either placebo (PL) or 50 mg losartan (LOS). Baseline GFR, RBF, and FF were higher in DM (P < 0.005). In the C group, PL + L-NAME caused declines in GFR (101 ± 3 to 90 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (931 ± 22 to 754 ± 31 ml·min⁻¹·1.73 m⁻²), and UNaV (158 ± 12 to 82 ± 18 µmol/min) and an increase in FF (0.19 ± 0.02 to 0.21 ± 02; P < 0.001), which were not influenced by LOS pretreatment (P > 0.05 for LOS + L-NAME-C vs. PL + l-NAME-C). In DM, PL + L-NAME resulted in exaggerated renal effects, with changes in GFR (128 ± 3 to 104 ± 3 ml·min⁻¹·1.73 m⁻²), RBF (1,019 ± 27 to 699 ± 34 ml·min⁻¹·1.73 m⁻²), UNaV (150 ± 13 to 39 ± 14 µmol/min), and FF (0.22 ± 0.03 to 0.26 ± 0.02) that were significantly greater vs. PL + L-NAME-C (P < 0.005). LOS pretreatment blunted GFR, RBF, FF, and UNaV responses to L-NAME in DM (P < 0.005 vs. PL + L-NAME-DM), resulting in a response profile that was similar to PL + L-NAME and LOS + L-NAME in C (P > 0.05). Renal responses to L-NAME in uncomplicated, type 1 DM are exaggerated vs. C, consistent with an upregulation of NO bioactivity. LOS, without effects in C, prevents the accentuated actions of L-NAME in DM, thus indicating an augmented role for NO-RAS interactions in renal hemodynamic function in DM.

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.

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.

Renal hemodynamic response to L-arginine in uncomplicated, type 1 diabetes mellitus: the role of buffering anions and tubuloglomerular feedback.

According to the "tubulocentric" hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute "distal" sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg(-1)·min(-1) l-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (-0.26 ± 0.07 mmol/min C vs. -0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min(-1)·1.73 m(-2)) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min(-1)·1.73 m(-2)). In contrast, with ARG.HCl, DDNa rose in both groups (P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased (P = 0.001, +219 ± 20 ml·min(-1)·1.73 m(-2) C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups (P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C (P = 0.001) and GFR, unchanged in C, declined in DM (-7.4 ± 0.9 ml·min(-1)·1.73 m(-2), P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction.

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.

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.

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.

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.