Beneficial effects of recombinant CER-001 high-density lipoprotein infusion in sepsis: results from a bench to bedside translational research project.

BACKGROUND: Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. METHODS: We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. RESULTS: CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. CONCLUSIONS: CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. TRIAL REGISTRATION: The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.

Intraoperative Examination of Retro-Areolar Margin is not Routinely Necessary During Nipple-Sparing Mastectomy for Cancer.

BACKGROUND: Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real advantage. METHODS: Consecutive patients undergoing NSM for cancer with omission of IERM according to institutional protocols from 2016 to 2021 were retrospectively analyzed. The decision to maintain or remove the Nipple-Areola Complex (NAC) after definitive pathology was taken at the multidisciplinary meeting. RESULTS: Among 162 women operated in the study period, the presence of neoplastic cells within 2 mm from the inked retroareolar margin (RAM) was detected at permanent pathology in 17 cases (10.5%). Nipple-Areola-Complex (NAC) was removed postoperatively in five patients (3%) for margins <1 mm, the other 12 were observed, whereas postoperative NAC necrosis required surgical removal in additional five cases (3%). The NAC was thus preserved in 152 of 162 patients (94%). At multivariate analysis, RAM ≤2 mm was associated with radiological tumor-to-nipple distance less than or equal to 1 cm (p = 0.04) and Ki67 label index ≥ 20 (p = 0.04), whereas multifocality/multicentricity showed a trend towards significance (p = 0.07). At a median follow-up of 46 months, five locoregional relapses occurred (3%), only one of them involving the NAC (0, 6%). Locoregional relapse and overall survival for patients with RAM > or < 2 mm were not different. CONCLUSIONS: IERM is not routinely necessary during NSM for cancer, because its omission is associated with a very low return to the operating room, it is oncologically safe, and associated pitfalls are avoided. Further studies are necessary to confirm these findings.

Cytomegalovirus-specific T cells restricted for shared and donor human leukocyte antigens differentially impact on cytomegalovirus reactivation risk after allogeneic hematopoietic stem cell transplantation.

After allogeneic hematopoietic stem cell transplantation (HSCT), the emergence of circulating cytomegalovirus (CMV)- specific T cells correlates with protection from CMV reactivation, an important risk factor for non-relapse mortality. However, functional assays measuring CMV-specific cells are time-consuming and often inaccurate at early time-points. We report the results of a prospective single-center, non-interventional study that identified the enumeration of Dextramerpositive CMV-specific lymphocytes as a reliable and early predictor of viral reactivation. We longitudinally monitored 75 consecutive patients for 1 year after allogeneic HSCT (n=630 samples). The presence of ≥0.5 CMV-specific CD8+ cells/mL at day +45 was an independent protective factor from subsequent clinically relevant reactivation in univariate (P<0.01) and multivariate (P<0.05) analyses. Dextramer quantification correlated with functional assays measuring interferon-γ production, and allowed earlier identification of high-risk patients. In mismatched transplants, the comparative analysis of lymphocytes restricted by shared, donor- and host-specific HLA revealed the dominant role of thymic-independent CMV-specific reconstitution. Shared and donor-restricted CMV-specific T cells reconstituted with similar kinetics in recipients of CMV-seropositive donors, while donor-restricted T-cell reconstitution from CMV-seronegative grafts was impaired, indicating that in primary immunological responses the emergence of viral-specific T cells is largely sustained by antigen encounter on host infected cells rather than by cross-priming/presentation by non-infected donor-derived antigen-presenting cells. Multiparametric flow cytometry and high-dimensional analysis showed that shared-restricted CMV-specific lymphocytes display a more differentiated phenotype and increased persistence than donor-restricted counterparts. In this study, monitoring CMV-specific cells by Dextramer assay after allogeneic HSCT shed light on mechanisms of immune reconstitution and enabled risk stratification of patients, which could improve the clinical management of post-transplant CMV reactivations.

MUC1 Expression Affects the Immunoflogosis in Renal Cell Carcinoma Microenvironment through Complement System Activation and Immune Infiltrate Modulation.

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.

Correlation between In Vitro Neutralization Assay and Serological Tests for Protective Antibodies Detection.

Serological assays are useful in investigating the development of humoral immunity against SARS-CoV-2 in the context of epidemiological studies focusing on the spread of protective immunity. The plaque reduction neutralization test (PRNT) is the gold standard method to assess the titer of protective antibodies in serum samples. However, to provide a result, the PRNT requires several days, skilled operators, and biosafety level 3 laboratories. Therefore, alternative methods are being assessed to establish a relationship between their outcomes and PRNT results. In this work, four different immunoassays (Roche Elecsys® Anti SARS-CoV-2 S, Snibe MAGLUMI® SARS-CoV-2 S-RBD IgG, Snibe MAGLUMI® 2019-nCoV IgG, and EUROIMMUN® SARS-CoV-2 NeutraLISA assays, respectively) have been performed on individuals healed after SARS-CoV-2 infection. The correlation between each assay and the reference method has been explored through linear regression modeling, as well as through the calculation of Pearson's and Spearman's coefficients. Furthermore, the ability of serological tests to discriminate samples with high titers of neutralizing antibodies (>160) has been assessed by ROC curve analyses, Cohen's Kappa coefficient, and positive predictive agreement. The EUROIMMUN® NeutraLISA assay displayed the best correlation with PRNT results (Pearson and Spearman coefficients equal to 0.660 and 0.784, respectively), as well as the ROC curve with the highest accuracy, sensitivity, and specificity (0.857, 0.889, and 0.829, respectively).

The expression of microRNAs and exposure to environmental contaminants related to human health: a review.

Environmental contaminants exposure may lead to detrimental changes to the microRNAs (miRNAs) expression resulting in several health effects. miRNAs, small non-coding RNAs that regulate gene expression, have multiple transcript targets and thereby regulate several signalling molecules. Even a minor alteration in the abundance of one miRNA can have deep effects on global gene expression. Altered patterns of miRNAs can be responsible for changes linked to various health outcomes, suggesting that specific miRNAs are activated in pathophysiological processes. In this review, we provide an overview of studies investigating the impact of air pollution, organic chemicals, and heavy metals on miRNA expression and the potential biologic effects on humans.Abbreviations: AHRR, aryl-hydrocarbon receptor repressor; AHR, aryl-hydrocarbon receptor; As, arsenic; BCL2, B-cell lymphoma 2; BCL2L11, B-cell lymphoma 2 like 11; BCL6, B-cell lymphoma 6; BPA, bisphenol A; CVD, cardiovascular diseases; CD40, cluster of differentiation 40; CCND1, Cyclin D1; CDKN1A, cyclin-dependent kinase inhibitor 1A; Cr, chromium; CTBP1, C-terminal binding protein 1; CXCL12, C-X-C motif chemokine ligand 12; DAZAP1, deleted in azoospermia associated protein 1; DEP, diesel exhaust particles; EGFR, epidermal growth factor receptor; eNOS, endothelial nitric oxide synthase; EVs, extracellular vesicles; FAK, focal adhesion kinase; FAS, fas cell surface death receptor; FOXO, forkhead box O; HbA1c, glycated hemoglobin; Hg, mercury; HLA-A, human leukocyte antigen A; HMGB, high-mobility group protein B; IFNAR2, interferon alpha receptor subunit 2; IL-6, interleukin-6; IRAK1, interleukin 1 receptor associated kinase 1; JAK/STAT, janus kinase/signal transducers and activators of transcription; MAPK, mitogen-activated protein kinase; miRNAs, microRNAs; MVs, microvesicles; NCDs, noncommunicable diseases; NFAT, nuclear factor of activated T cells; NFkB, nuclear factor kappa B; NRF2, nuclear factor, erythroid-derived 2; NRG3, neuregulin 3; O3, ozone; OP, organophosphorus pesticides; PAHs, polycyclic aromatic hydrocarbons; Pb, lead; PCBs, polychlorinated biphenyls; PDCD4, programmed cell death 4; PDGFB, platelet derived growth factor subunit beta; PDGFR, platelet-derived growth factor receptor; PI3K/Akt, phosphoinositide-3-kinase/protein kinase B; PKA, protein kinase A; PM, particulate matter; PRKCQ, protein kinase C theta; PTEN, phosphatase and tensin homolog; SORT1, sortilin 1; TGFß, transforming growth factor-ß; TLR, toll-like receptor; TNF, tumor necrosis factors; TRAF1, tumor necrosis factors-receptor associated factors 1; TRAP, traffic-related air pollution; TREM1, triggering receptor expressed on myeloid cells 1; TRIAP1, TP53 regulated inhibitor of apoptosis 1; VCAM-1, vascular cell adhesion molecule 1; VEGFA, vascular endothelial growth factor A; XRCC2, X-ray repair cross complementing 2; YBX2, Y-box-binding protein 2; ZEB1, zinc finger E-box-binding homeobox 1; ZEB2, zinc finger E-box-binding homeobox 2; 8-OH-dG, 8-hydroxy-guanine.

Predictive Machine Learning Models and Survival Analysis for COVID-19 Prognosis Based on Hematochemical Parameters.

The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan-Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; HR=17.963 (95% CI 6.548-49.277, p < 0.001) for death, HR=1.789 (95% CI 1.000-3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; HR=1.765 (95% CI 1.141-2.729, p < 0.05) for death, HR=1.481 (95% CI 0.895-2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients.

DPSIR framework priorities and its application to forest management: a fuzzy modeling.

The main aim of this research was to quantify the parameters related to forest situation (according to DPSIR framework) using decision-making processes and fuzzy methods in the Zagros forests of Iran. In this study, the situation factors (e.g., socioeconomic, biophysical, and environmental factors) were evaluated by fuzzy analytic hierarchy process (FAHP) using [Formula: see text]-cuts in addition to the Chang method for fuzzy pairwise comparisons. The results of the study clearly illustrate that the decision-making process is the most important input in forest management planning in the Zagros forests, Iran. In such situations, decision-making techniques can be of great help in differentiating the factors influencing decision-making and policy-making for these forests. We found that [Formula: see text]-cuts could improve the quality of the decision-making process, but only after secondary analysis. Initially, we did not find any significant difference in the results between [Formula: see text]-cuts and research results, but using the differences in rankings, we could identify a significant difference. We propose that this method, which requires lengthy calculations to get the answer, should only be used by forest managers when the quality of the results and the difference between the parameters are very important to them; otherwise, they may be able to achieve the same desired results in a much easier way.

Adherence to Mediterranean diet of children living in small Southern Italian villages.

A cross-sectional study was conducted in the primary schools of five small villages of Salento Peninsula to evaluate the adherence to the Mediterranean Diet (MD) of 282 6-8-years old children in relation to lifestyles and socio-economic factors. The parents of children completed a self-administered questionnaire to evaluate the prevalence of personal, behavioural and socio-economic factors of their sons. Children's anthropometric measurements were also taken. The adherence to the MD was assessed using the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED). The chi-square test was used to detect any differences among groups of children. Overall, 27.0% of children showed low adherence to the MD (KIDMED ≤3), 59.6% medium adherence (KIDMED 4-7) and 13.5% high adherence (KIDMED ≥8). The adherence to the MD was associated with the educational level (whether graduated or not) of the mother and the occupational status (whether employed or not) of both parents.

Monitoring Systems and Numerical Models to Study Coastal Sites.

The present work aims at illustrating how the joint use of monitoring data and numerical models can be beneficial in understanding coastal processes. In the first part, we show and discuss an annual dataset provided by a monitoring system installed in a vulnerable coastal basin located in Southern Italy, subjected to human and industrial pressures. The collected data have been processed and analysed to detect the temporal evolution of the most representative parameters of the inspected site and have been compared with recordings from previous years to investigate recursive trends. In the second part, to demonstrate to what extent such type of monitoring actions is necessary and useful, the same data have been used to calibrate and run a 3D hydrodynamic model. After this, a reliable circulation pattern in the basin has been reproduced. Successively, an oil pollution transport model has been added to the hydrodynamic model, with the aim to present the response of the basin to some hypothetical cases of oil spills, caused by a ship failure. It is evident that the profitable prediction of the hydrodynamic processes and the transport and dispersion of contaminants strictly depends on the quality and reliability of the input data as well as on the calibration made.

Experimental Setup and Measuring System to Study Solitary Wave Interaction with Rigid Emergent Vegetation.

The aim of this study is to present a peculiar experimental setup, designed to investigate the interaction between solitary waves and rigid emergent vegetation. Flow rate changes due to the opening and closing of a software-controlled electro-valve generate a solitary wave. The complexity of the problem required the combined use of different measurement systems of water level and velocity. Preliminary results of the experimental investigation, which allow us to point out the effect of the vegetation on the propagation of a solitary wave and the effectiveness of the measuring system, are also presented. In particular, water level and velocity field changes due to the interaction of the wave with rigid vegetation are investigated in detail.

Molecular characterization of Cryptococcus neoformans and Cryptococcus gattii from environmental sources and genetic comparison with clinical isolates in Apulia, Italy.

The present study investigated the environmental distribution of Cryptococcus neoformans and C. gattii species complex molecular types, mating types and sequence types in Apulia, a region of Southern Italy. A total of 2078 specimens from arboreal and animal sources were analyzed. The percentage of positive samples was similar among both arboreal and animal specimens: 4.2% vs. 5.1% for C. neoformans species complex and 0.6% vs. 1.4% for C. gattii species complex. Molecular typing identified 78 isolates as VNI (76 αA and two aA), one as AD-hybrid αADa, and 16 as VGI aB. VNI isolates presented 10 different sequence types (STs) and VGI isolates two. The most frequent STs among C. neoformans and C. gattii species complex isolates were ST23 (51%) and ST156 (90%), respectively. Comparison with molecular types and STs results obtained from 21 clinical isolates collected in Apulia showed that one C. neoformans VNI clinical isolate shared an identical sequence type of one arboreal isolate (ST61) and that one C. gattii VGI clinical isolate matched with the main ST (ST156) present in the environment. In addition, molecular type VNIV was found only among clinical isolates and was absent in the investigated environmental area. In conclusion, the present study identified which C. neoformans and C. gattii species complex genotypes are circulating in Apulia, defined their ecological niches and revealed the relationship with clinical cases. It represents a basal study for addressing future investigations and public health interventions in the region.

Meteo and Hydrodynamic Measurements to Detect Physical Processes in Confined Shallow Seas.

Coastal sites with typical lagoon features are extremely vulnerable, often suffering from scarce circulation. Especially in the case of shallow basins subjected to strong anthropization and urban discharges, it is fundamental to monitor their hydrodynamics and water quality. The proper detection of events by high performance sensors and appropriate analysis of sensor signals has proved to be a necessary tool for local authorities and stakeholders, leading to early warning and preventive measures against environmental degradation and related hazards. At the same time, assessed datasets are not only essential to deepen the knowledge of the physical processes in the target basin, but are also necessary to calibrate and validate modelling systems providing forecasts. The present paper aims to show how long-term and continuous recordings of meteorological and hydrodynamic data, collected in a semi-enclosed sea, can be managed to rapidly provide fundamental insights on its hydrodynamic structure. The acquired signals have been analyzed in time domain, processed and finally, correlated. The adopted method is simple, feasible and easily replicable. Even if the results are site-dependent, the procedure is generic, and depends on having good quality available data. To show how this might be employed, a case study is examined. In fact, it has been applied to a coastal system, located in Southern Italy, where two monitoring stations are placed in two interconnected basins. The inferred results show that the system is not wind dominated, and that the annual trends in the wind regime, wave spreading and current circulation are not independent, but rather reiterate. These deductions are of great interest as a predictive perspective and for numerical modelling.

Environmental distribution of Cryptococcus neoformans and C. gattii around the Mediterranean basin.

In order to elucidate the distribution of Cryptococcus neoformans and C. gattii in the Mediterranean basin, an extensive environmental survey was carried out during 2012-2015. A total of 302 sites located in 12 countries were sampled, 6436 samples from 3765 trees were collected and 5% of trees were found to be colonized by cryptococcal yeasts. Cryptococcus neoformans was isolated from 177 trees and C. gattii from 13. Cryptococcus neoformans colonized 27% of Ceratonia, 10% of Olea, Platanus and Prunus trees and a lower percentage of other tree genera. The 13 C. gattii isolates were collected from five Eucalyptus, four Ceratonia, two Pinus and two Olea trees. Cryptococcus neoformans was distributed all around the Mediterranean basin, whereas C. gattii was isolated in Greece, Southern Italy and Spain, in agreement with previous findings from both clinical and environmental sources. Among C. neoformans isolates, VNI was the prevalent molecular type but VNII, VNIV and VNIII hybrid strains were also isolated. With the exception of a single VGIV isolate, all C. gattii isolates were VGI. The results confirmed the presence of both Cryptococcus species in the Mediterranean environment, and showed that both carob and olive trees represent an important niche for these yeasts.

Experimental study of a vertical jet in a vegetated crossflow.

Aquatic ecosystems have long been used as receiving environments of wastewater discharges. Effluent discharge in a receiving water body via single jet or multiport diffuser, reflects a number of complex phenomena, affecting the ecosystem services. Discharge systems need to be designed to minimize environmental impacts. Therefore, a good knowledge of the interaction between effluents, discharge systems and receiving environments is required to promote best environmental management practice. This paper reports innovative 3D flow velocity measurements of a jet discharged into an obstructed crossflow, simulating natural vegetated channel flows for which correct environmental management still lacks in literature. In recent years, numerous experimental and numerical studies have been conducted on vegetated channels, on the one hand, and on turbulent jets discharged into unvegetated crossflows, on the other hand. Despite these studies, however, there is a lack of information regarding jets discharged into vegetated crossflow. The present study aims at obtaining a more thorough understanding of the interaction between a turbulent jet and an obstructed crossflow. In order to achieve such an objective, a series of laboratory experiments was carried out in the Department of Civil, Environmental, Building Engineering and Chemistry of the Technical University of Bari - Italy. The physical model consists of a vertical jet discharged into a crossflow, obstructed by an array of vertical, rigid, circular and threaded steel cylinders. Analysis of the measured flow velocities shows that the array of emergent rigid vegetation significantly affects the jet and the ambient flow structures. It reduces the mean channel velocity, allowing the jet to penetrate higher into the crossflow. It significantly increases the transversal flow motion, promoting a major lateral spreading of the jet within the crossflow. Due to the vegetation array effects, the jet undergoes notable variations in its vortical structure. The variation of the flow patterns affects the mixing process and consequently the dilution of pollutants discharged in receiving water bodies.

Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients.

In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.

Interleukin-1 receptor-related protein ST2 and mitral valve repair outcome in patients with chronic degenerative mitral regurgitation.

BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is markedly upregulated in cultured cardiomyocytes subjected to mechanical strain. Serum soluble ST2 (sST2) levels can be detected in patients with acute myocardial infarction and severe chronic heart failure. This study sought to assess for the first time the activation of the ST2 pathway in patients with severe chronic degenerative mitral regurgitation. MATERIALS AND METHODS: Serum sST2 levels were measured in 20 patients scheduled for mitral valve (MV) repair at baseline, at the end of the intervention, on postoperative day 1, at hospital discharge, and after 6 months. Patients also underwent measurement of N-terminal pro-brain natriuretic peptide and echocardiographic evaluation at each time point. RESULTS: At baseline, sST2 was detected in 10 (50%) patients (mean value, 60 ± 74 pg/mL; range, 0-234 pg/mL; median, 8 pg/mL). MV repair was performed successfully in all patients. Cardiac surgery with cardiopulmonary bypass was associated with a rapid and transient increase in sST2 levels. Patients with baseline higher versus lower sST2 levels (≥ 8 vs. < 8 pg/mL) had significantly higher levels of sST2 on postoperative day 1 (1,050 ± 593 vs. 440 ± 312 pg/mL; p = 0.009). At follow-up, patients with preoperative sST2 ≥ 8 pg/mL had significantly higher ejection fraction (EF) (64.7 ± 5.8 vs. 57.6 ± 5.9; p = 0.03) and lower left ventricular end-diastolic diameter (LVEDD) (50.6 ± 5.8 vs. 56 ± 4.2; p = 0.03) compared with patients with preoperative sST2 < 8 pg/mL. CONCLUSION: Preoperative ST2 activation, evidenced by the presence of serum sST2 levels, is present in half of the patients with chronic degenerative mitral regurgitation and is associated with higher levels of EF and lower levels of LVEDD after MV repair.

Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea.

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.