Kidney disease and psoriasis: novel evidences beyond old concepts

Psoriasis is an immune-mediated inflammatory disease for a long time considered as a type of pathology characterized by an exclusive skin involvement. Recently it has been shown that patients affected by this disease have a higher risk of developing comorbidities such as cardiovascular diseases, arterial hypertension, diabetes mellitus, and metabolic syndrome. Even the kidneys can be affected by psoriasis through three different mechanisms: immune-mediated renal damage, drug-related renal damage and chronic renal damage. Renal function should be monitored periodically to minimize the risk of renal adverse events.     

Synthetic isoxazole as antiplatelet agent

Abstract

Nine synthetic isoxazoles were evaluated as antiplatelet agents and studied the possible mechanism of more active compound. The initial screening was evaluating all compounds against platelet aggregation assays. The most active compound was isoxazole 8 showing an inhibition of platelet aggregation around 70%. In subsequent experiments, ADP and collagen were used as agonists to explore the possible inhibitory mechanisms of isoxazole 8 in platelet aggregation and secretion. We reported the effect of isoxazole 8 for reducing the expression of inflammatory markers, such as soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin), on activated platelets. Of this form, an inhibition of sCD40L and sP-selectin can prevent the onset of an atherosclerotic lesion.     

Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging

BackgroundIschemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging–derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.ObjectivesThe authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.MethodsBrain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).ResultsPrevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.ConclusionsPrevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.     

Dilated Cardiomyopathy and Role of Antithrombotic Therapy

BackgroundThere is no consensus as to whether anticoagulation has a favorable risk:benefit in reducing thromboembolic events in patients with heart failure (HF) secondary to dilated cardiomyopathy who do not suffer from atrial fibrillation or primary valvular disease.Methods and ResultsThe literature reviewed on this topic included most recent and ongoing studies that assessed the use of anticoagulation for this population. Several large retrospective studies showed an increased risk of thromboembolic events among patients with depressed left ventricular function. The relative risk of stroke in individuals with HF from all causes was found to be 4.1 for men and 2.8 for women, but confounding comorbidities (such as atrial fibrillation and coronary artery disease) were commonly present. Currently, there are no randomized prospective trials to guide the use of antithrombotics for these patients, and the risk of bleeding secondary to anticoagulation has limited the use of oral anticoagulants for prevention of thrombosis. Among patients with HF, increasing age directly correlates with both major bleeding and thromboembolic events, with a 46% relative risk of bleeding for each 10-year increase in age older than 40 years.ConclusionsTo date, there is no agreement on appropriate antithrombotic treatment (if any) for primary thromboembolism prophylaxis in patients with dilated cardiomyopathy with sinus rhythm. In recent years, several promising prospective trials were terminated prematurely due to inadequate enrollment. The Warfarin Aspirin-Reduced Cardiac Ejection Fraction trial may provide evidence regarding the use of anticoagulation for patients with decreased myocardial function.     

Influence of exercise test on platelet function in patients with coronary arterial disease: A systematic review

Background:Exercise test (ET) may have adverse effects on platelet function and induce acute thrombotic events in patients with coronary artery disease (CAD). The aim of this study is to investigate the platelet function and evaluate the risk of thrombotic events in CAD patients during ET.Methods:Pubmed, Embase, Cochrane Library, and Web of Science were searched for a systematic review from initiation to October 2019. The inclusion criteria were controlled clinical trails as study design; investigating platelet function in CAD patients during ET; with ET carried out by treadmill or bicycle ergometer; written in English. Included articles were screened based on title/abstract and full-text review by 2 independent reviewers. Platelet aggregation (PA), platelet surface expression of CD62p and PAC-1, plasma levels of platelet factor 4 (PF4) and beta-thromboglobulin (β-TG) were evaluated before and after ET.Results:Eighteen articles were included out of the 427 references initially identified. In most of the studies included ET was terminated because of limited symptoms. Prior to ET, no difference in platelet aggregation was observed in CAD patients compared with healthy controls in majority of the studies, with or without the treatment with Aspirin. Dual anti-platelet therapy suppressed adenosine diphosphate (ADP)-induced platelet aggregation at rest. After ET, platelet aggregation, the serum levels of β-thromboglobulin were found unchanged in majority of studies and platelet factor-4 were found unchanged in half of studies. The expression of platelet surface markers were elevated by ET in a few study.Conclusion:Symptom-limited exercise test did not affect platelet function in patients with coronary artery disease; however exercise to higher intensity may induce platelet activation.     

Metformin combined with dipeptidyl peptidase-4 inhibitors or metformin combined with sulfonylureas in patients with type 2 diabetes: A real world analysis of the South Korean national cohort

AimsWe explored the risks associated with metformin plus sulfonylurea (MET + SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET + DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities.MethodsThis retrospective cohort study is based on the South Korean National Health Insurance Service–National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET + SU or MET + DPP4i between July 1, 2008 and December 31, 2013. The risk of hypoglycemia, CVD events and all-cause mortality was examined using Cox's proportional hazard modeling and propensity score matching.ResultsOverall, 5693 patients with a mean of 2.6 comorbidities in addition to diabetes were included. Compared with MET + SU, MET + DPP4i treatment was associated with a lower risk of hypoglycemia, CVD events and all-cause mortality; adjusted HRs (95% CI), 0.39 (0.18–0.83), 0.72 (0.54–0.97), and 0.64 (0.39–1.05), respectively. Propensity score matching showed comparable results. In further subgroup analyses according to comorbidity type and number, MET + DPP4i was associated with less CVD events and all-cause mortality compared to MET + SU. This increased with more complex comorbid status.ConclusionsIn T2D patients with comorbidities, MET + DPP4i treatment is associated with lower risks of CVD events and all-cause mortality compared with MET + SU, independent of type or number of comorbidities. A more complex comorbid status further increases this effect.     

Gender Differences in Platelet Reactivity in Diabetic Patients Receiving Dual Antiplatelet Therapy

BackgroundIncreased comorbidities and a perceived high-bleeding risk often prevent the use of dual antiplatelet therapy (DAPT) in female patients. However, more aggressive antiplatelet treatment would certainly offer additional outcome benefits in coronary artery disease, especially among diabetic patients. The aim of the present study was to evaluate the gender differences in high-residual on treatment platelet reactivity (HRPR) among diabetic patients treated with DAPT.MethodsOur population is represented by a consecutive cohort of diabetic patients treated with DAPT (ASA + clopidogrel, ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30–90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry and in diabetic patients naïve to antiplatelet therapy, by light transmission aggregometry, surface expression of P-selectin and plasma concentration of Thromboxane B2.ResultsWe included 472 patients, 113 (23.9%) women. Female gender was associated with more advanced age, and increased comorbidities. Mean platelet reactivity did not differ according to gender. The rate of HRPR was similar in women as compared to men (for ASA: adjusted OR[95%CI] = 0.59[0.27–1.33], p = 0.21, for ADP-antagonists: adjusted OR[95%CI] = 1.24[0.25–1.80], p = 0.27), however, the benefits of the new ADP-antagonists on platelet reactivity were lower in women than in men (p interaction = 0.01).No impact of gender on platelet reactivity was confirmed among 50 diabetic patients naïve to antiplatelet therapy.ConclusionsAmong diabetic patients receiving dual antiplatelet therapy gender does not affect platelet reactivity or high-on treatment platelet reactivity. However, the enhanced platelet inhibition provided by the new-ADP antagonists of new-ADP antagonists could be mitigated in women.     

Platelet function in cutaneous diseases

Blood platelets participate actively in immune-inflammatory processes. Responding to the variety of stimuli such as cell activation leads to the release of several mediators, including RANTES, platelet factor 4, beta-thromboglobulin, thymus and activation-regulated chemokine (TARC/CCL17), serotonin and arachidonic acid metabolites. It also affects the expression of immunomodulatory and adhesive molecules, including CD154 and P-selectin. Immune–inflammatory processes associated with skin diseases could induce platelet activation, which, in turn, would contribute to acceleration and modulation of these processes. Activated platelets are capable of facilitating leukocyte rolling in the skin and the release of skin inflammation mediators. Changes in platelet function and behaviour may occur in certain types of skin inflammatory conditions and platelets might then be an important effector cell of the skin immune system, contributing to the pathogenesis of some skin inflammatory disorders. The changes in platelet activity and reactivity have been demonstrated to show distinctly different pathogenic mechanisms in cutaneous diseases, such as urticaria, atopic eczema/dermatitis syndrome and psoriasis. Considering the risk of cardiovascular events, some of them seem to be of clinical significance. This contribution is a brief outline of the present knowledge of the platelet function in dermal disorders.     

Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

Infección gastrointestinal por Aeromonas: incidencia y su posible relación con la enfermedad inflamatoria intestinal

IntroductionAeromonas can cause several diseases in humans, with gastroenteritis accounting for most cases. The role of Aeromonas as a pathogen in human enterocolitis has been questioned in recent years.ObjectiveTo determine the incidence of gastrointestinal infection caused by Aeromonas in our area and its possible relationship to inflammatory bowel disease.Patients and methodsThis was a retrospective observational study. All adult patients with a positive stool culture for Aeromonas were identified between January 2015 and December 2017 at Hospital Galdakao-Usansolo (Vizcaya, Spain).ResultsNinety-eight patients were identified (median age 62 years; 51% women). Therefore, the incidence in our area was 32 cases per 10⁵ inhabitants per year. Eleven per cent of them had been previously diagnosed with inflammatory bowel disease (four with ulcerative colitis and seven with Crohn's disease). Patients with inflammatory bowel disease more often received immunosuppressive therapy. Conversely, patients without inflammatory bowel disease suffered from more comorbidities. We also found comorbidity to be the risk factor most associated with Aeromonas infection.ConclusionAeromonas infection is a common gastrointestinal infection that may occur in both immunocompetent and immunocompromised patients. Immunosuppression is a significant factor in inflammatory bowel disease patients, while comorbidity seems to confer a higher risk on patients without this disease.     

Platelet activation in patients with Familial Mediterranean Fever

Increased platelet activation and aggregation are central processes in the pathophysiology of atherosclerosis. Increased platelet activity is associated with increased platelet volume. Mean platelet volume (MPV), a determinant of platelet function, is a newly emerging risk factor for atherothrombosis. Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory febrile attacks of serosal and synovial membranes. Recently few studies have shown that FMF is associated with increased atherosclerosis risk. The present study was designed to evaluate levels of MPV in FMF patients compared with healthy subjects. We selected 35 FMF patients and 35 healthy control subjects matched for age, gender, and body mass index. Metabolic parameters and MPV levels were measured in all groups. Metabolic parameters were not different among the study groups (p > 0.05). The levels of MPV were significantly higher in the FMF group than in the control group (8.6 ± 0.9 fl vs 7.8 ± 0.5 fl, p = 0.001). The MPV levels were negatively correlated with duration of colchicine treatment (r = ?0.40, p = 0.017). Also MPV levels showed positive correlation with delay of diagnosis (r = 0.58, p = 0.001). In conclusion, our results suggest that patients with FMF tend to have an increased platelet activation. Increased platelet activity could contribute to increasing the atherosclerotic risk in FMF patients.     

An increased intake of thiamine diminishes the risk of metabolic syndrome in the Korean population with various comorbidities

Background and aimsThere is growing evidence that thiamine supplementation could reverse non-communicable diseases such as diabetes and cardiovascular diseases. However, the role of thiamine in metabolic syndrome (MetS) remains unclear. We hypothesized whether an increased intake of thiamine diminishes the risk of MetS in the Korean population with various comorbidities. This study aimed to assess the association between thiamine intake and MetS among adults with comorbidities.Methods57,523 eligible participants aged over 18 years between 2009 and 2019 were recruited to obtain data on sociodemographic characteristics, medical history, current medications, lifestyle, and family history. A 24-h recall was used to determine thiamine intake. Odds ratio (OR) for MetS was calculated for log2-transformed thiamine intake values, subsequently predicting the risk of MetS based on the marginal effect.ResultsThe risk of MetS was significantly higher in subjects with comorbidities than in those without comorbidities. A doubling of daily thiamine intake was significantly associated with a decrease in MetS among adults with comorbidities by 7% (OR 0.93; 95%CI 0.89–0.97).ConclusionsThe potential health benefits result from the intake of thiamine through an ordinary diet in the clinical management of MetS. Therefore, there is an ongoing need to look into these links between thiamine supplementation and MetS in well-characterized cohorts of participants with comorbidities.     

Increased serum interleukin-6 level as a predictive biomarker for atrial fibrillation: A systematic review and meta-analysis

BackgroundAtrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy.MethodsWe conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF.ResultsA total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p<0.001) and all-cause mortality (RR 2.35, CI 95% 2.09-2.65, p<0.001).ConclusionA higher level of IL-6 may predict a greater number of long-term thromboembolic events and bleeding events, ACS events and mortality in AF patients. Further studies such as the cut-off point of IL-6 need to be conducted in the future.     

Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation

Background Female patients with atrial fibrillation (AF) experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA₂DS₂VASc score. New onset AF (often associated with tachycardia) also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide (NO) signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Methods Interactions were sought in 87 AF patients between the extent of adenosine diphosphate (ADP)-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein (Txnip) was also evaluated. Results Analysis of covariance confirmed the presence of physiological antagonism between platelet ADP and NO responses [F (1, 74) = 12.212, P < 0.01], while female sex correlated with impaired NO responses independent of platelet aggregability [F (2, 74) = 8.313, P < 0.01]. Admission heart rate correlated directly with platelet aggregation (r = 0.235, P < 0.05), and inversely with NO response (r = -0.331, P < 0.01). Txnip expression varied neither with gender nor with heart rate. Conclusions These results indicate that gender and heart rate are independent determinants of platelet function. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.     

Platelet function in cutaneous diseases

Blood platelets participate actively in immune-inflammatory processes. Responding to the variety of stimuli such as cell activation leads to the release of several mediators, including RANTES, platelet factor 4, beta-thromboglobulin, thymus and activation-regulated chemokine (TARC/CCL17), serotonin and arachidonic acid metabolites. It also affects the expression of immunomodulatory and adhesive molecules, including CD154 and P-selectin. Immune-inflammatory processes associated with skin diseases could induce platelet activation, which, in turn, would contribute to acceleration and modulation of these processes. Activated platelets are capable of facilitating leukocyte rolling in the skin and the release of skin inflammation mediators. Changes in platelet function and behaviour may occur in certain types of skin inflammatory conditions and platelets might then be an important effector cell of the skin immune system, contributing to the pathogenesis of some skin inflammatory disorders. The changes in platelet activity and reactivity have been demonstrated to show distinctly different pathogenic mechanisms in cutaneous diseases, such as urticaria, atopic eczema/dermatitis syndrome and psoriasis. Considering the risk of cardiovascular events, some of them seem to be of clinical significance. This contribution is a brief outline of the present knowledge of the platelet function in dermal disorders.     

Consensus recommendations on managing the selected comorbidities including cardiovascular disease,osteoporosis, and interstitial lung disease in rheumatoid arthritis

Background:Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities.Methods:The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities.Results:Based on experts’ consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities.Conclusions:These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.     

Prasugrel: A Novel Platelet ADP P2Y12 Receptor Antagonist

The antiplatelet drug prasugrel is one of the new generations of thienopyridines, drugs that inhibit the platelet P2Y₁₂ receptor. It is becoming clear that there is variability in individual responses to antiplatelet agents such as clopidogrel, which may limit their efficacy and widespread utility. A number of controversies remain, such as varied definitions of “nonresponders” to antiplatelet therapy, the optimal means of assessing platelet function, and the potential capacity of in vivo platelet function studies to predict future clinical events. Prasugrel provides more rapid and consistent platelet inhibition than does clopidogrel, yet its clinical utility is under scrutiny. We aim to review the available data evaluating the efficacy and safety of this novel antiplatelet agent.     

Assessment of Cardiovascular Risk in Transgender Patients Presenting for Gender-Affirming Care

BackgroundThe transgender population is rapidly growing in the United States and abroad. Transgender men and women are marginalized as a result of their transgender status, with resultant health repercussions. This and other factors such as increased substance use, mental health disorders, violence, and chronic stress may place transgender individuals at higher risk for cardiovascular disease. Additionally, many transgender patients pursue gender-affirming hormone therapy, which has been linked to increased rates of some cardiovascular events such as metabolic syndrome, venous thromboembolism, and stroke. Despite the likelihood of elevated cardiovascular risk in this population, there is a paucity of published data about the cardiovascular risk of this population.MethodsWe present baseline cardiovascular data from a transgender population at a large tertiary care center prior to the initiation of hormone therapy.ResultsThe described transgender population had much higher rates of mental health disorders and substance use than the general population. Furthermore, there were high rates of undiagnosed and untreated comorbidities, such as hypertension and dyslipidemia, that increase risk for cardiovascular disease. Baseline risk assessment using the ASCVD (Atherosclerotic Cardiovascular Disease) and QRISK3 calculators showed higher-than-expected cardiovascular risk, particularly given the young age of our patient population.ConclusionsTransgender individuals are at high baseline cardiovascular risk. These data help fill some important knowledge gaps in this patient subgroup, and provide us with much-needed data to help guide our management and counseling of individuals seeking this type of care.     

TP receptor activation and inhibition in atherothrombosis: the paradigm of diabetes mellitus

Patients with type 2 diabetes mellitus are characterized by increased incidence of cardiovascular events and enhanced thromboxane-dependent platelet activation. Urinary enzymatic TXA₂ metabolites (such as 11-dehydro-TXB₂), reflecting the whole TXA₂ biosynthesis by platelet and extra-platelet sources, are significantly increased in diabetes with the absolute post-aspirin values of 11-dehydro-TXB₂ in diabetics being comparable to non-aspirated controls and such residual TXA₂ biosynthesis despite low-dose aspirin treatment is predictive of vascular events in high-risk patients. Thus, elevated urinary 11-dehydro-TXB₂ levels identify patients who are partially insensitive to aspirin and who may benefit from alternative antiplatelet therapies or treatments that more effectively block in vivo TXA₂ production or activity. Potential mechanisms relatively insensitive to aspirin include extraplatelet, nucleate sources of TXA₂ biosynthesis, possibly triggered by inflammatory stimuli, or lipid peroxidation with enhanced generation of F2-isoprostane (reflecting ongoing in vivo oxidative stress) than can activate platelets via the platelet TP receptor thus escaping inhibition by aspirin. In fact, aspirin does not inhibit isoprostane formation. Moreover, intraplatelet or extraplatelet thromboxane generation may be only partly inhibited by aspirin under certain pathological conditions, at least at the usual low doses given for cardiovascular protection. TXA₂ receptors (TP) are expressed on several cell types and exert antiatherosclerotic, antivasoconstrictive and antithrombotic effects, depending on the cellular target. Thus, targeting TP receptor, a common downstream pathway for both platelet and extraplatelet TXA₂ as well as for isoprostanes, may be an useful antithrombotic intervention in clinical settings, such as diabetes mellitus characterized by persistently enhanced thromboxane-dependent platelet activation.     

Potential beneficial role of probiotics on the outcome of COVID-19 patients: An evolving perspective

Background and aimsProbiotics can support the body’s systems in fighting viral infections. This review is aimed to focus current knowledge about the use of probiotics as adjuvant therapy for COVID-19 patients.MethodsWe performed an extensive research using the PubMed-LitCovid, Cochrane Library, Embase databases, and conducting manual searches on Google Scholar, Elsevier Connect, Web of Science about this issue.ResultsWe have found several papers reporting data about the potential role of probiotics as well as contrasting experimental data about it.ConclusionsMost data show good results demonstrating that probiotics can play a significant role in fighting SARS-CoV-2 infection, also compared with their use in the past for various diseases. They seem effective in lowering inflammatory status, moreover in patients with chronic comorbidities such as cancer and diabetes, improving clinical outcomes.