Nutritional Strategies To Improve VRE Control.

The rise of Vancomycin-resistant enterococci (VRE) strains among cellular therapy recipients raises concerns due to increased morbidity, mortality, and hospitalization costs, particularly impacting transplanted patients with diminished survival expectations. Recent research linking lactose to Enterococcus growth and graft-versus-host disease (GVHD) emphasizes the need for data on reducing lactose in the diets of VRE-carrying patients, especially in cellular therapy contexts like CAR-T or allogeneic hematopoietic stem cell transplantation. Responding to elevated VRE positivity rates in rectal swabs among patients in our BMT Unit, a unique nutritional strategy was implemented, introducing lactose-free milk and strictly enforcing lactose-free diets. This approach resulted in a significant reduction in VRE carriers, with a 16% positivity rate in the Lactose Group versus 3.6% in the Lactose-Free Group, as of June 2023. These results indicate the potential efficacy of this innovative nutritional strategy in high-risk departments, such as BMT Units and Intensive Care Units, with implications for reducing isolation strategies and inappropriate antibiotic use in cases of VRE colonization.

Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response.

Human Metapneumovirus (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, per se, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.

The Synthetic Dipeptide Pidotimod Shows a Chemokine-Like Activity through CXC Chemokine Receptor 3 (CXCR3).

In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid, PDT) is a synthetic dipeptide, which possesses immunomodulatory properties and exerts a well-defined pharmacological activity against infections, but its real mechanism of action is still undefined. Here, we show that PDT is capable of activating tyrosine phosphorylation-based cell signaling in human primary monocytes and triggering rapid adhesion and chemotaxis. PDT-induced monocyte migration requires the activation of the PI3K/Akt signaling pathway and chemokine receptor CXCR3. Indeed, a mAb to CXCR3 and a specific receptor inhibitor suppressed significantly PDT-dependent chemotaxis, and CXCR3-silenced primary monocytes lost responsiveness to PDT chemoattraction. Moreover, our results highlighted that the PDT-induced migratory activity is sustained by the CXCR3A isoform, since CXCR3-transfected L1.2 cells acquired responsiveness to PDT stimulation. Finally, we show that PDT, as CXCR3 ligands, is also able to direct the migration of IL-2 activated T cells, which express the highest levels of CXCR3 among CXCR3-expressing cells. In conclusion, our study defines a chemokine-like activity for PDT through CXCR3A and points on the possible role that this synthetic dipeptide may play in leukocyte trafficking and function. Since recent studies have highlighted diverse therapeutic roles for molecules which activates CXCR3, our findings call for an exploration of using this dipeptide in different pathological processes.

Breathlessness, but not cough, suggests chronic obstructive pulmonary disease in elderly smokers with stable heart failure.

Chronic obstructive pulmonary disease (COPD) is a common comorbidity of heart failure (HF), but remains often undiagnosed, and we aimed to identify symptoms predicting COPD in HF. As part of an observational, prospective study, we investigated stable smokers with a confirmed diagnosis of HF, using the 8-item COPD-Assessment-Test (CAT) questionnaire to assess symptoms. All the items were correlated with the presence of COPD, and logistic regression models were used to identify independent predictors. 96 HF patients were included, aged 74, 33% with COPD. Patients with HF and COPD were more symptomatic, but only breathlessness when walking up a hill was an independent predictor of COPD (odds ratio = 1.33, p = 0.0484). Interestingly, COPD-specific symptoms such as cough and phlegm were not significant. Thus, in elderly smokers with stable HF, significant breathlessness when walking up a hill is most indicative of associated COPD, and may indicate the need for further lung function evaluation.

Use of adjunct cardiovascular therapy in patients hospitalised for acute exacerbations of COPD.

In real-life practice, acute exacerbation of COPD is often treated as a cardiopulmonary syndrome http://ow.ly/uAnk30luMYz.

[Lung and heart interaction: chronic obstructive pulmonary disease and ischemic heart disease]. / Interazioni cuore-polmoni: la broncopneumopatia cronica ostruttiva e la cardiopatia ischemica.

The interaction between the lung and the heart is a vast, complex, and fascinating topic and, from a clinical point of view, disorders of the one often influence and promote disorders of the other. This is especially true for chronic diseases, with chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD) representing a classic example. Epidemiologic data indicate that cardiovascular diseases are frequent in patients with COPD, and vice versa. Accordingly, rates of IHD in COPD vary from 4% up to 60%, while, on the other hand, COPD has been reported in up to 30% of patients with coronary artery disease. Interestingly, prevalence rates are generally significantly higher compared to control populations. COPD and IHD share common risk factors, such as cigarette smoking, physical inactivity, unhealthy lifestyle, and advancing age, which may justify this epidemiologic link. However, other mechanisms such as altered systemic inflammatory response and negative effects of acidosis and hypoxia are probably involved in the correlation between COPD and IHD. Clinically, certain symptoms such as worsening dyspnea, chest tightness, reduced physical activity, and low exercise tolerance are common to both lung and cardiac diseases, and their interpretation may be challenging in clinical practice. However, the identification of COPD in patients with known IHD, and vice versa, is very important, due to higher risk of worse outcomes, lower quality of life, higher hospitalization and, ultimately, higher mortality. Similarly, therapeutic management may be challenging, due to apparently contrasting indications, such as the use of beta-blockers in IHD, and beta2-agonists in COPD, and possible cardiac side effects of bronchodilators.In this narrative review we will discuss these topics, providing a comprehensive evaluation of these two relevant comorbidities.

Human lung epithelial cells support human metapneumovirus persistence by overcoming apoptosis.

Human metapneumovirus (hMPV) has been identified as a major cause of lower respiratory tract infection in children. Epidemiological and molecular evidence has highlighted an association between severe childhood respiratory viral infection and chronic lung diseases, such as asthma and chronic obstructive pulmonary disease. Currently, animal models have demonstrated the ability of hMPV to persist in vivo suggesting a role of the virus in asthma development in children. However, mechanisms involved in hMPV persistence in the respiratory tract are not yet understood. In the present study we monitored hMPV infection in human alveolar epithelial A549 cells in order to understand if the virus is able to persist in these cells upon acute infection. Our data show that hMPV initially induces an apoptotic process in A549 cells through poly (ADP-ribose) polymerase 1 cleavage, caspase-3/7 activation and Wee1 activity. The hMPV-infected cells were then able to overcome the apoptotic pathway and cell cycle arrest in G2/M by expressing B-cell lymphoma 2 and to acquire a reservoir cell phenotype with constant production of infectious virus. These findings provide evidence of the ability of hMPV to persist in alveolar epithelial cells and help in understanding the mechanisms responsible for hMPV persistence in the human respiratory tract.

Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care.

Chronic obstructive pulmonary disease (COPD) is a global health issue with high social and economic costs. Concomitant chronic cardiac disorders are frequent in patients with COPD, likely owing to shared risk factors (e.g., aging, cigarette smoke, inactivity, persistent low-grade pulmonary and systemic inflammation) and add to the overall morbidity and mortality of patients with COPD. The prevalence and incidence of cardiac comorbidities are higher in patients with COPD than in matched control subjects, although estimates of prevalence vary widely. Furthermore, cardiac diseases contribute to disease severity in patients with COPD, being a common cause of hospitalization and a frequent cause of death. The differential diagnosis may be challenging, especially in older and smoking subjects complaining of unspecific symptoms, such as dyspnea and fatigue. The therapeutic management of patients with cardiac and pulmonary comorbidities may be similarly challenging: bronchodilators may have cardiac side effects, and, vice versa, some cardiac medications should be used with caution in patients with lung disease. The aim of this review is to summarize the evidence of the relationship between COPD and the three most frequent and important cardiac comorbidities in patients with COPD: ischemic heart disease, heart failure, and atrial fibrillation. We have chosen a practical approach, first summarizing relevant epidemiological and clinical data, then discussing the diagnostic and screening procedures, and finally evaluating the impact of lung-heart comorbidities on the therapeutic management of patients with COPD and heart diseases.

Coronary artery disease concomitant with chronic obstructive pulmonary disease.

BACKGROUND: Numerous epidemiologic studies have linked the presence of chronic obstructive pulmonary disease (COPD) to coronary artery disease (CAD). However, prevalence, pathological processes, clinical manifestations and therapy are still debated, as progress towards uncovering the link between these two disorders has been hindered by the complex nature of multimorbidity. METHODS: Articles targeting CAD in patients with COPD were identified from the searches of MEDLINE and EMBASE databases in July 2013. Three authors reviewed available evidence, focusing on the latest development on disease prevalence, pathogenesis, clinical manifestations and therapeutic strategies. Both clinical trial and previous reviews have been included in this work. RESULTS: The most accredited hypothesis asserts that the main common risk factors, that is, cigarette smoke and ageing, elicit a chronic low-grade systemic inflammatory response, which affects both cardiovascular endothelial cells and airways/lung parenchyma. The development of CAD in patients with COPD potentiates the morbidity of COPD, leading to increased hospitalizations, mortality and health costs. Moreover, correct diagnosis is challenging and therapies are not clearly defined. CONCLUSIONS: Evidence from recently published articles highlights the importance of multimorbidity in patient management and future research. Moreover, many authors emphasize the importance of low-grade systemic inflammation as a common pathological mechanism and a possible future therapeutic target.

Early and long-term outlook of percutaneous coronary intervention for bifurcation lesions in young patients.

BACKGROUND: Coronary artery disease is most common in older patients, but may occur in younger subjects. The outlook of young patients after percutaneous coronary intervention (PCI) of challenging lesion subsets such as coronary bifurcations, is not established. We thus aimed to appraise the early and long-term results of PCI for bifurcations in young patients. METHODS: A multicenter, retrospective study was conducted enrolling consecutive patients undergoing bifurcation PCI between 2002 and 2006 in 22 Italian centers. Patients were divided in 2 groups: age ≤ 45 years, and age > 45 years. The primary end-point was long-term rate of major adverse cardiac events (MACE). RESULTS: 4,314 patients were included: 195 (4.5%) in the younger group, and 4119 (95.5%) in the older group. 30-day outcomes did not show significant differences in MACE rates, with 1.0% in the ≤ 45 years group and 2.1% in the >45 years group (p=0.439), with death in 0.5% and 1.2% (p=0.388). At long-term follow-up (24.4 ± 15.1 months), younger patients showed similar rates of MACE, (12.8% vs. 16.6%, p=0.161), myocardial infarction (3.1% vs. 3.7%, p=0.633), target lesion revascularization (11.3% vs. 12.5%, p=0.627), or stent thrombosis (1.5% vs. 2.8%, p=0.294), despite an increased risk of death in older patients (1.0% vs. 5.0%, p=0.012). Even at extensive multivariable analysis, younger patients still faced a similar risk of MACE (HR=0.78 [0.48-1.27], p=0.318). CONCLUSIONS: Despite their low age, young patients undergoing PCI for bifurcation face a significant risk of early and late non-fatal adverse events. Thus, they should not be denied careful medical management and follow-up.

Sex-related differences in carotid plaque features and inflammation.

OBJECTIVE: Severe carotid stenosis is a frequent cause of stroke in both men and women. Whereas several sex-related comparisons are available on coronary atherosclerosis, there are few data appraising gender-specific features of carotid plaques. We aimed to systematically compare the pathology and inflammatory features of carotid plaques in men vs women. METHODS: Carotid plaque specimens were collected from patients undergoing surgical endarterectomy for asymptomatic or symptomatic carotid stenosis. Histologic analysis was performed, as well as measurements of plaque composition and inflammation. RESULTS: A total of 457 patients were included (132 women, 325 men). Baseline analyses showed a greater prevalence of hypercholesterolemia, hypertension, and former smoking status in women, despite a higher Framingham Heart Score in men (all P < .05). Women had a lower prevalence of thrombotic plaques, smaller percentage area of necrotic core, and hemorrhage extension (all P < .05). Plaque inflammation analysis showed a lower concentration of inflammatory and, in particular, of macrophage foam cells in the plaque cap of women (both P < .05). These differences were, however, no longer significant at multivariable analysis, including several baseline features, such as symptom status and stenosis severity. CONCLUSIONS: Carotid plaques seem significantly different in women and men, but the main drivers of such pathologic differences are baseline features, including stenosis severity and symptom status.

Circumflex coronary artery agenesis associated with thoracic great vessels anomalies.

Coronary artery anomalies are identified in approximately 1% of patients who undergo angiography; among these, circumflex branch agenesis represents 0.003%. A 38-year-old woman was brought to our emergency department with clinical findings suggestive of acute myocardial infarction. Absence of circumflex branch was reported during angiography. Further analysis showed great vessel abnormalities: the presence of a left superior vena cava, a left arterial trunk of abnormal origin, and a small cerebral aneurysm. To our knowledge, this is the only reported case with such vascular anomalies.