Background: Hypercoagulability, complement activation and endothelial perturbation characterize sever COVID-19. After disease remission, a proportion of convalescent subjects still experience post-COVID-19 symptoms. No information is available on persistence of hemostatic alterations in this setting. Bergamo city, represents one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting CCP donors. Aims: In a large cohort of CCP donors, we aimed to characterize biomarkers of hypercoagulability and of endothelial perturbation in order to find associations with disease severity, demographic characteristics, and anti-SARS-CoV-2 antibody levels. Methods : Candidate CCP donors were tested for the anti-SARSCoV-2 antibodies, including anti-S IgG antibodies (Anti-S Ab) and anti-N IgG antibodies (Anti-N Ab). In addition, the following plasma biomarkers were assessed: fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, and von Willebrand factor (vWF). Results: 425 CCP candidates (275M/150F, age range 19-67 years) were admitted to donation. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab ( p <0.001). Among hemostatic parameters, levels of vWF antigen, vWF activity and protein C were significantly higher in CCP donors who had severe COVID-19 compared to donors who had non-severe COVID-19 ( p <0.001). Furthermore, vWF levels positively correlated with anti-S Ab levels (vWF-antigen r=0.216 vWF-activity r=0.257 and vWFRiCof r=0.226, p <0.01). Conclusions: Our data show that gender, age and severe disease can be predictors of an increased immunological response. Furthermore, convalescent subjects show a persistently high vWF levels, suggesting a persistence of the endothelial activation, despite of clinical disease remission.

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is an immune-mediated life-threatening thrombotic microangiopathy (TMA). Daily therapeutic plasma exchange (TPE) and the optimized use of rituximab have dramatically improved the overall prognosis, however the rate of disease recurrence remains high. Acute-phase treatment and specific predictors of relapse can be relevant for an optimal patient management. Aims: In a large multicenter cohort of aTTP patients, we aimed to analyze the effect of acute-phase treatment on disease recurrence and to identify predictive variables of relapse. Methods: From 2002 to 2018, 325 TMA were referred to our Centers. A complete ADAMTS13 activity deficiency (<10%) was diagnostic for TTP in 163 patients. An anti-ADAMTS13 Ab titer >15U/L was considered positive and identified aTTP cases. Seventy-four aTTP patients with complete medical records were enrolled into the study and prospectively monitored. Complete response (CR) to treatment was defined as platelets >150x109/L for >2 days and LDH normalization, lasting for 30 days; a suboptimal response included exacerbation (EX) = recurrent disease within 30 days after reaching CR; and refractoriness (REF) = no treatment response by day 30. Results: aTTP patient characteristics at diagnosis are shown in the Table. Sixty-three patients were evaluated for treatment response. Two (3%) early deaths were due to myocardial infarction and diffuse rectal ischemia after 7 and 10 days from diagnosis, respectively. Forty patients (64%) obtained a CR after a median time to response (mTTR) of 10 days and a median number of TPE (mTPE) of 7; 21 (33%) obtained a suboptimal response: 13 EX (mTTR 31 days, mTPE 13), and 8 REF (mTTR 42.5, mTPE 19). Thirteen patients with a suboptimal response to TPE were treated with rituximab, all obtaining CR. TTR to 1st line treatment <13 days significantly correlated with a sustained CR (p = 0.004). At remission, 57% of patients showed normal levels (>50%) of ADAMTS13 activity, while 20% a moderate (21–50%), 10% a severe (10–20%), and 11% a complete (<10%) deficiency. A complete or partial recovery of ADAMTS13 activity was associated to negative Ab levels in 90% of cases. Twenty-one patients (34%) relapsed, 14 of them had multiple relapses. Median follow-up was 7 years. Patients were evaluated for predictive parameters of disease recurrence. By multivariate analysis, the association of ADAMTS13 activity ≤20% with a high anti-ADAMTS-13 titer during remission, and a TTR to 1st line treatment ≥13 days, were independent prognostic factors of relapse (p = 0.003 and p = 0.004, respectively). Furthermore, the use of rituximab in patients with a suboptimal TPE response significantly reduced relapse rate (p = 0.002). By Cox regression analysis, patients with ADAMTS13 activity ≤20% plus anti-ADAMTS13 Ab titer >15U/L at remission had an increased risk of relapse (HR 1.98, CI 95% 1.087–3.614; p < 0.02).Summary/Conclusion: In conclusion, our study shows that the association of a low ADAMTS13 activity with high anti-ADAMTS13 antibodies is highly predictive of disease relapse. Moreover, a shorter time to 1st line CR achievement and the salvage use of rituximab in suboptimal responders to TPE significantly reduces relapse. These observations support the use of new therapeutic strategies able to provide faster responses to 1st line TPE treatment in these patients.

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

The case of a patient with large pseudoaneurysm of the mitral-aortic intervalvular fibrosa following a blunt chest trauma is presented. A two dimensional echocardiographic study revealed a large aneurysmal sac situated between the posterior aortic root and the left atrium, which expanded in systole and partially collapsed in diastole. An echo-free space which represented the mouth of the aneurysm was seen just below the posterior aortic cusp in the junctional zone between the two valves, called mitral-aortic intervalvular fibrosa. Nuclear magnetic resonance imaging showed a better resolution of the echocardiographic feature. Cardiac catheterization and surgery confirmed the diagnosis.

The authors relate their own experience with 24 hr Holter monitoring in course of cardiac rehabilitation after coronary bypass surgery as well as after valvular replacement. As regards patients after coronary surgery they report the experience they got in the evaluation of heart rate trend and cardiac arrhythmias as well as in silent ischemia study. About this last problem 116 patients with signs of ischemia both in stress test and in Holter recording are considered out of 491 who had undergone coronary surgery. Ischemia during 24 hr Holter monitoring develops at an heart rate lower than effort ischemia. Holter monitoring proves to be very useful also in patients after valvular replacement to study arrhythmias and to check drugs' efficacy. After displaying the results concerning arrhythmias of 24 hr Holter electrocardiograms recorded in 207 randomized patients who had undergone valvular replacement 15 days before, the authors dwell upon the use of Holter electrocardiography in 82 valvular patients after pharmacological cardioversion and show that major arrhythmias get a clear reduction thanks to rehabilitation.

The first approach to treatment of dyslipidaemia is with diet. Currently, modified soybean protein is often included in the diet. A study was made of 32 patients with types IIa and IIb dyslipidaemia to see what changes in blood lipids could be induced by a simple low fat diet and a diet with modified soybean protein substituted for part of the animal protein. After six weeks on the initial low fat diet, all of the patients had lower total cholesterol and triglyceride levels, but there were no significant changes in the high density lipoprotein-cholesterol levels. The same diet was continued for eight weeks by 19 of the patients, who continued to improve. The 13 patients who had shown the least response to the initial simple low protein diet were given a diet in which the animal protein was partially replaced with modified soybean protein. This diet further decreased the total cholesterol.

The effectiveness of Nitroderm TTS 5 and Nitroderm TTS 10 in stable effort-induced angina pectoris was assessed by measuring the tolerance of 20 selected in-patients to cycloergometric symptom-limited tests. During the week preceding the trial previous anti-anginal treatment was gradually withdrawn except for short-acting nitrates. Patients were also familiarized with ergometric laboratory environment. The trial started with a 24-h control period when placebo was given single-blind to each patient. A double-blind cross-over design was then followed, two groups of 10 patients each being subjected successively to two sequences of therapy. By means of the double-dummy technique, Nitroderm TTS 5 or Nitroderm TTS 10 and matching placebos were applied simultaneously once daily for 24 h on two different days. Resting heart rate and blood pressure were measured before starting each exercise test, which was performed 3 h after placebo as well as 3 and 24 h after Nitroderm TTS application. The results of the tests were evaluated in terms of maximum workload, duration of exercise and total work performed for each of the two doses administered and compared with the corresponding baseline values. When compared with placebo both Nitroderm TTS doses produced a significant change (P less than 0.01) in the assessment variables. After application of the active treatment, duration of exercise, total work performed and maximal workload were increased while lying and standing blood pressures were decreased. There was no significant difference between the two doses of Nitroderm TTS in the assessment variables, except for systolic blood pressure and lying heart rate 3 and 24 h, respectively, post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

The present investigation was undertaken to evaluate the effects of Dilazep, a new antiplatelet and coronary dilating drug, on the exercise tolerance of patients who had suffered previous myocardial infarction and were participating in a cardiac rehabilitation programme. Seventy-two patients were enrolled in the study. They were randomly allocated to two groups of 36 subjects; patients in group A took Dilazep, 300 mg daily; patients in group B took acetylsalicylic acid, 100 mg daily, or dipyridamole, 300 mg daily. Before and after treatment all patients underwent two maximal or symptom limited cycloergometer stress tests, respectively 30 and 60 days after the episode of acute myocardial infarction. Total exercise time, maximum workload reached, heart rate, blood pressure, double product and oxygen pulse were measured. In both groups a significant increase in both total exercise time and maximum workload reached was recorded at the second stress test; this may reflect a greater degree of physical conditioning due to the rehabilitation programme. In group A patients total exercise time increased from 457.12 +/- 5.36 sec to 588.28 +/- 8.24 sec (p less than 0.005), in group B patients it increased from 459.18 +/- 6.11 sec to 547.43 +/- 7.47 sec (p less than 0.005). The mean values of maximum workload reached increased in group A from 4512.14 +/- 116.47 kgm to 5288.57 +/- 145.38 kgm (p less than 0.005), and in group B from 4522.22 +/- 108.42 kgm to 5098 +/- 137.51 kgm (p less than 0.005). Thus the exercise tolerance improved more in patients taking Dilazep than in those taking acetylsalicylic acid or dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)