Interleukin-1 Blockers in Recurrent and Acute Pericarditis: State of the Art and Future Directions.

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.

Clostridium tetani Infection in a Geriatric Patient: Do Not Let Your Guard Off!

Tetanus is an infectious disease caused by Clostridium tetani toxin. Although easily preventable through vaccination, over 73,000 new infections and 35,000 deaths due to tetanus occurred worldwide in 2019, with higher rates in countries with healthcare barriers. Here, we present a clinical case of C. tetani infection in an 85-year-old patient. Patient robustness and high functional reserve before infection are favorable predictors of survival for an otherwise fatal disease. However, the patient did not experience any severe complications. Therefore, this report is a strong call for tetanus vaccination.

Rapid resolution of severe pericardial effusion using anakinra in a patient with COVID-19 vaccine-related acute pericarditis relapse: a case report.

Background: Pericarditis, along with myocarditis, is being increasingly reported after the coronavirus disease 2019 (COVID-19) vaccine, but the best treatment strategy in this specific setting is still unclear. Case summary: We report a case of acute pericarditis after the second dose of mRNA COVID-19 vaccine with recurrence of large pericardial effusion after a previous pericardiocentesis and anti-inflammatory drugs tapering. The patient was successfully treated with the recombinant interleukin-1 receptor antagonist anakinra, with full reabsorption of the pericardial effusion and an abrupt drop of the inflammatory markers within 72 h. The patient was discharged a few days later, with a further decrease of the inflammatory markers and no residual symptoms. Discussion: Anakinra is being increasingly used in the treatment of recurrent pericarditis due to its capability to interrupt the autoinflammatory response leading to deleterious cytokine storms. On account of its high efficacy and rapid onset, it has been reported to rapidly reverse large inflammatory pericardial effusions. Pericarditis and myocarditis have been reported after the COVID-19 vaccine, but this is the first case of COVID-19 vaccine-related pericarditis and pericardial effusion successfully treated with anakinra, avoiding a second pericardiocentesis.

Early introduction of anakinra improves acute pericarditis and prevents tamponade in Staphylococcal sepsis.

The clinical response to anakinra observed by this patient concurrently treated with antibiotics indirectly confirms the potentially pathogenic role of IL-1 in maintaining the pericardial disease and shows how IL-1 blockade might allow avoiding the pericardiocentesis procedure. The report supports the hypothesis that anakinra is an effective and safe tool in the early treatment of acute pericarditis of presumed bacterial origin nonresponding to targeted antibiotic therapy.

Late haemodynamic and functional consequences of radial artery removal on the forearm circulation.

BACKGROUND: We aimed at evaluating the late haemodynamic and functional consequences on the forearm circulation of radial artery removal for coronary artery bypass grafting. METHODS: Ten years after surgery we performed basal and stress echo-Doppler evaluation of the forearm circulation, baseline and stress transcutaneous oxymetry and determination of reactive oxygen metabolites in the operated and control arm in 20 asymptomatic patients submitted to radial artery removal. RESULTS: The peak systolic velocity of the ulnar artery of the operated side was significantly higher than the control site. Transcutaneous oxymetry revealed asymptomatic hand ischemia at moderate level of muscular effort in the operated arm, but reactive oxygen metabolites measurement did not differ between the two arms. CONCLUSIONS: Even in patients with good ulnar compensation, radial artery removal leads to subtle degree of hand ischemia in conditions of sustained muscular effort. Although the clinical significance of this observation remains to be determined, this finding can have important implications for conduit selection in patients involved in manual activities.

Reduction of oxidative stress by compression stockings in standing workers.

BACKGROUND: Healthy workers who stand for prolonged periods show enhanced production of reactive oxygen species (ROS) in their systemic circulation. Oxidative stress is thought to be a risk factor for chronic venous insufficiency and other systemic diseases. AIM: To evaluate the effectiveness of compression stockings in the prevention of oxidative stress at work. METHODS: ROS and venous pressure of the lower limbs were measured in 55 theatre nurses who stood in the operating theatre for >6 h, 23 industrial ironers who stood for up to 5 h during their shift and 65 outpatient department nurses and 35 laundry workers who acted as controls. Subjects and controls were examined on two consecutive days before and after work and with and without compression stockings. RESULTS: Without compression stockings, lower limb venous pressure increased significantly after work in all subjects and controls (P < 0.001), while only operating theatre nurses showed significantly higher mean levels of ROS (P < 0.001). There was no significant difference in venous pressures and ROS levels after work in subjects or controls when wearing compression stockings. CONCLUSIONS: Our data suggest a preventive role of compression stockings against oxidative stress in healthy workers with a standing occupation.

Chronic compensatory increase in ulnar flow and accelerated atherosclerosis after radial artery removal for coronary artery bypass.

BACKGROUND: Only scant information is available on the chronic consequences of radial artery removal for coronary artery bypass surgery on forearm circulation. METHODS: Twenty-five patients submitted to radial artery removal for coronary artery bypass were submitted to serial Doppler echocardiographic evaluation of the flow and morphology of the forearm arteries. RESULTS: The peak systolic velocity of the ulnar artery of the operated side was significantly higher than that of the control site. The intimal-medial thickness of the ulnar artery was always significantly higher on the operated side, and this difference reached statistical significance at 10 years' follow-up. There was a significantly higher prevalence of atherosclerotic plaques in the ulnar artery of the operated versus control arm (7/25 vs 0/25, P = .03). CONCLUSION: Radial artery removal for coronary artery bypass surgery leads to a chronic increase in ulnar flow accompanied by increased intimal-medial thickness and accelerated atherosclerotic disease. These findings might have potentially important implications for surgical indications and patient management.

Treatment of ischemic ulcers of the lower limbs with alprostadil (prostaglandin E1).

BACKGROUND: Hemodynamic, hemorheologic, and metabolic changes are main determinants in the genesis of ischemic leg ulcers. Because prostaglandin E1 (alprostadil) could successfully counteract these changes, it has been intravenously used in the treatment of this disease. OBJECTIVE: The aim of this study was to evaluate the efficacy of alprostadil in the treatment of ischemic ulcers and to compare subcutaneous with intravenous administration. METHODS: Eighty patients were enrolled. Twenty-five were treated by injecting low doses of alprostadil around ischemic ulcers of the leg and saline solution intravenously and 25 were treated with intravenous alprostadil and local injections of saline solution; the control group was composed of 30 patients who received saline solution around the ulcers and intravenously. RESULTS: All patients showed a statistically significant improvement in ulcer diameter, pain, and transcutaneous oxygen pressure compared to the control group. No relevant differences in the clinical outcome in the two treated groups were found, but patients treated with subcutaneous alprostadil experienced no side effects and showed higher values of transcutaneous oxygen pressure. CONCLUSIONS: Both intravenous and local subcutaneous alprostadil are useful in the treatment of ischemic leg ulcers, but subcutaneous administration is less expensive and easier to perform.

Long saphenous vein stripping reduces local level of reactive oxygen metabolites in patients with varicose disease of the lower limbs.

Long saphenous vein (LSV) stripping is the most common surgical procedure in patients affected by varicose disease of the lower limbs. Reactive oxygen metabolites (ROM) generation plays a crucial role in chronic venous insufficiency (CVI). The aim of this study was to investigate whether ROM generation is increased in patients affected by varicose disease versus healthy controls and whether LSV stripping has a positive effect on the local production of ROM. The local production of ROM was assessed measuring hydroperoxides in the blood collected from the leg of 30 patients consecutively undergoing LSV stripping and 30 controls. In both the patient group and the control group, the test was repeated 30 days later. We found that ROM levels before surgery are higher in varicose vein patients than in controls ( p <.0001) and that ROM are significantly reduced 30 days after LSV stripping ( p <.0001). At that time point, no significant differences between patients and controls was found. We also found that sex and age do not affect ROM concentration in patients and controls, either before or after surgery. In conclusion, our data indicate that CVI is characterized by significant oxidative stress and that LSV stripping is able to normalize local production of ROM in patients with varicose disease of the lower limbs. We suggest that measurement of ROM might be useful to test the positive effects of LSV stripping in these patients.

Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population.

Alzheimer's disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with Alzheimer's disease in an Italian population [corrected].

Interleukin-6 (IL-6) is a multifunctional cytokine playing a crucial role in inflammation and tissue injury. A role for this molecule in neurodegeneration and Alzheimer's disease (AD) has been proposed. The aim of this study was to evaluate the association between a common polymorphism of the IL-6 gene promoter and AD in the Italian population. We found that the frequency of the GG genotype was significantly higher in AD patients than controls on both univariate ( rho< 0.0001) and multivariate analysis ( rho< 0.0001). In contrast, the CC genotype seems to be associated with a reduced risk of disease ( rho< 0.0001). Our data indicate that the IL-6 gene polymorphism is associated with AD in Italians and confirm that IL-6 is crucial in the pathophysiology of neurodegenerative disorders.

Association between intercellular adhesion molecule-1 E/K gene polymorphism and probable vascular dementia in humans.

Intercellular adhesion molecule-1 (ICAM-1) is implicated in the pathogenesis of ischemic cardiovascular disorders, including cerebral ischemia. A common polymorphism of the ICAM-1 gene (K469E) has been recently reported. In this case-control study, we evaluated the association between this polymorphism and vascular dementia (VD) by studying 107 patients affected by probable VD and 115 age- and sex-matched controls. The frequency of the EE genotype was significantly higher in VD patients than controls (P=0.009). Logistic regression analysis indicated that the presence of the EE genotype significantly increased the risk of VD (odds ratio 3.25, P=0.024). Our findings support the hypothesis that ICAM-1 plays a role in the physiopathology of ischemic cerebrovascular disorders and suggest that genetic polymorphisms of ICAM-1 might be clinically important in the development and progression of neurodegenerative diseases.

-174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study.

The aim of this study was to evaluate the association between the -174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and multi-infarct dementia (MID). We studied a group of 122 patients affected by MID and 134 age- and sex-matched controls and evaluated classical risk factors for MID, as well as the distribution of IL-6 alleles and genotypes by polymerase chain reaction and restriction enzyme analysis. The distribution of IL-6 genotypes was 63 GG, 47 GC, 12 CC in patients with MID and 29 GG, 58 GC, 47 CC in control subjects. The GG genotype was significantly more common in the MID group (P<0.0001), while the CC genotype was more common in control patients (P<0.0001). Logistic regression analysis indicated that the presence of GG genotype significantly increases the risk of MID (odds ratio 9.1 [3.1-26.1], P<0.0001). This study indicates a strong association between the -174 G/C polymorphism of the IL-6 gene and MID. Our data support the hypothesis that IL-6 and inflammatory mechanisms are important in the pathophysiology of the vascular changes responsible for cognitive deterioration.