Research

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26 pages, 2419 KiB

Open AccessArticle

Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock

by Marta Reina-Couto, Marisa Santos-Oliveira, Patrícia Pereira-Terra, Carolina Silva-Pereira, Janete Quelhas-Santos, Álvaro Duarte, Sandra Martins, Paula Serrão, Cláudia Camila Dias, Manuela Morato, João T. Guimarães, Roberto Roncon-Albuquerque, José-Artur Paiva, António Albino-Teixeira and Teresa Sousa

Biomedicines 2022, 10(11), 2845; https://doi.org/10.3390/biomedicines10112845 - 08 Nov 2022

Cited by 1 | Viewed by 1403

Abstract

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin–angiotensin–aldosterone system, and cardiac, renal, respiratory, and [...] Read more.

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin–angiotensin–aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1–2 (admission), 3–4, and 5–8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-α, IL-1β, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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8 pages, 1597 KiB

Open AccessArticle

Impact of COVID-19 Infection, Vaccination, and Serological Response in Immune Thrombocytopenic Purpura Patients: A Single-Center Global Analysis

by Cristina Dainese, Federica Valeri, Marco Bardetta, Carola Sella, Annamaria Porreca, Alessandra Valpreda, Fabrizia Pittaluga, Giulio Mengozzi, Benedetto Bruno and Alessandra Borchiellini

Biomedicines 2022, 10(11), 2674; https://doi.org/10.3390/biomedicines10112674 - 23 Oct 2022

Cited by 2 | Viewed by 1153

Abstract

Both SARS-CoV-2 infection and vaccination have raised concern in immune-mediated diseases, including immune thrombocytopenic purpura (ITP) considering risk of de novo ITP development and ITP recurrence. Here, we report on data from a single-center retrospective–prospective collection aiming to evaluate platelet (plt) dynamics in [...] Read more.

Both SARS-CoV-2 infection and vaccination have raised concern in immune-mediated diseases, including immune thrombocytopenic purpura (ITP) considering risk of de novo ITP development and ITP recurrence. Here, we report on data from a single-center retrospective–prospective collection aiming to evaluate platelet (plt) dynamics in patients (pts) with chronic ITP after COVID-19 infection (before and after vaccination) and after the first, second and third vaccine doses. Furthermore, we analyzed the serological response after the first two doses of COVID-19 vaccination. A total of 64 pts currently followed for chronic ITP who experienced COVD-19 infection and/or vaccination with an available plt count before and after such events were included in the analysis. A low incidence of ITP exacerbation following vaccine sessions (6–16%) was observed in comparison with a high frequency of exacerbation and rescue treatment necessity after COVID-19 infection in unvaccinated pts (83%). Moreover, the lower ITP exacerbation rate observed in infected pts previously vaccinated (18%) suggests further protective effects in this population. Finally, a high seroconversion rate was observed, confirming data reported in previously published studies on immune cytopenia and rheumatological diseases, but more evidence is awaited to establish the clinical impact of serological response. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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12 pages, 1428 KiB

Open AccessArticle

Effects of Reversal of Hypotension on Cerebral Microcirculation and Metabolism in Experimental Sepsis

by Fabio Silvio Taccone, Fuhong Su, Xinrong He, Lorenzo Peluso, Katia Donadello, Sabino Scolletta, Daniel De Backer and Jean-Louis Vincent

Biomedicines 2022, 10(4), 923; https://doi.org/10.3390/biomedicines10040923 - 18 Apr 2022

Cited by 1 | Viewed by 1644

Abstract

The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < [...] Read more.

The effects of reversal of hypotension on the cerebral microcirculation, oxygenation, and metabolism in septic shock remain unclear. In 12 sheep, peritonitis was induced by injection of feces into the abdominal cavity. At the onset of septic shock (mean arterial pressure (MAP) < 65 mmHg, unresponsive to fluid challenge), a norepinephrine infusion was titrated in eight sheep to restore a MAP ≥ 75 mmHg; the other four sheep were kept hypotensive. The microcirculation of the cerebral cortex was evaluated using side-stream dark-field video-microscopy. Brain partial pressure of oxygen (PbtO₂) was measured, and cerebral metabolism was assessed using microdialysis. All animals developed septic shock after a median of 15 (14–19) h. When MAP was raised using norepinephrine, the PbtO₂ increased significantly (from 41 ± 4 to 55 ± 5 mmHg), and the cerebral lactate/pyruvate ratio decreased (from 47 ± 13 to 28 ± 4) compared with values at shock onset. Changes in the microcirculation were unchanged with restoration of MAP and the glutamate increased further (from 17 ± 11 to 23 ± 16 μM), as it did in the untreated animals. In septic shock, the correction of hypotension with vasopressors may improve cerebral oxygenation but does not reverse the alterations in brain microcirculation or cerebral metabolism. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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11 pages, 2109 KiB

Open AccessArticle

Testosterone as a Biomarker of Adverse Clinical Outcomes in SARS-CoV-2 Pneumonia

by Lorenzo Marinelli, Guglielmo Beccuti, Marco Zavattaro, Serena Cagnina, Iacopo Gesmundo, Chiara Bona, Chiara Lopez, Silvia Scabini, Francesca Canta, Simone Mornese Pinna, Tommaso Lupia, Cataldo Di Bisceglie, Federico Ponzetto, Fabio Settanni, Francesco Giuseppe De Rosa, Ezio Ghigo and Giovanna Motta

Biomedicines 2022, 10(4), 820; https://doi.org/10.3390/biomedicines10040820 - 31 Mar 2022

Cited by 8 | Viewed by 2020

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic–pituitary–gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with [...] Read more.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect testicles. Lower testosterone levels have been associated with worse clinical outcomes and higher mortality. Our objective was to evaluate the hypothalamic–pituitary–gonadal axis of men admitted with SARS-CoV-2 pneumonia and its link with the pneumonia-treatment intensification. Short-term changes in hormonal parameters were also assessed. Methods: Men admitted with SARS-CoV-2 pneumonia were recruited in two different hospitals in Piedmont, Italy. In all patients, the assessment of total testosterone (TT), calculated free testosterone (cFT), gonadotropins, inhibin B (InhB), and other biochemical evaluations were performed at admission (T0) and before discharge (T1). Through a review of medical records, clinical history was recorded, including data on pneumonia severity. Results: Thirty-five men (median age 64 [58–74] years) were recruited. Lower TT and cFT levels at T0 were associated with CPAP therapy (p = 0.045 and 0.028, respectively), even after adjusting for age and PaO₂/FIO₂ ratio in a multivariable analysis. In those discharged alive, lower TT and cFT levels were associated with longer hospital stay (p < 0.01). TT, cFT, and InhB were below the normal range at T0 and significantly increased at T1 (TT 1.98 [1.30–2.72] vs. 2.53 [1.28–3.37] ng/mL, p = 0.038; cFT (0.0441 [0.0256–0.0742] vs. 0.0702 [0.0314–0.0778] ng/mL, p = 0.046; InhB 60.75 [25.35–88.02] vs. 77.05 [51.15–134.50], p < 0.01). Conclusions: Both TT and cFT levels are associated with adverse clinical outcomes in men admitted with SARS-CoV-2 pneumonia. As TT, cFT and InhB levels increase before discharge, short-term functional recovery of steroidogenesis and an indirect improvement of spermatozoa functional status could be hypothesized. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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13 pages, 1368 KiB

Open AccessArticle

Prognostic Value of Mid-Regional Proadrenomedullin Sampled at Presentation and after 72 Hours in Septic Patients Presenting to the Emergency Department: An Observational Two-Center Study

by Paolo Bima, Giorgia Montrucchio, Valeria Caramello, Francesca Rumbolo, Stefania Dutto, Sarah Boasso, Anita Ferraro, Luca Brazzi, Enrico Lupia, Adriana Boccuzzi, Giulio Mengozzi, Fulvio Morello and Stefania Battista

Biomedicines 2022, 10(3), 719; https://doi.org/10.3390/biomedicines10030719 - 19 Mar 2022

Cited by 8 | Viewed by 1770

Abstract

The prognostic value of mid-regional proADM (MR-proADM) in septic patients presenting to the emergency department (ED) is not well established. In this prospective observational study enrolling septic patients evaluated in two EDs, MR-proADM was measured at arrival (t0) and after 72 h (t72). [...] Read more.

The prognostic value of mid-regional proADM (MR-proADM) in septic patients presenting to the emergency department (ED) is not well established. In this prospective observational study enrolling septic patients evaluated in two EDs, MR-proADM was measured at arrival (t0) and after 72 h (t72). MR-proADM_%change was calculated as follows: (MR-proADM_t72h − MR-proADM_t0)/MR-proADM_t0. In total, 147 patients were included in the study, including 109 with a final diagnosis of sepsis and 38 with septic shock, according to the Sepsis-3 criteria. The overall 28-day mortality (outcome) rate was 12.9%. The AUC for outcome prognostication was 0.66 (95% CI 0.51–0.80) for MR-proADM_t0, 0.77 (95% CI 0.63–0.92) for MR-proADM_t72 and 0.74 (95% CI 0.64–0.84) for MR-proADM_%change. MR-proADM_t0 ≥ 2.78 nmol/L, MR-proADM_t72 ≥ 2.7 nmol/L and MR-proADM_%change ≥ −15.2% showed statistically significant log-rank test results and sensitivity/specificity of 81/65%, 69/80% and 75/70% respectively. In regression analysis, MR-proADM_%change was a significant outcome predictor both in univariate and multivariate analysis, after adjustment for age, SOFA and APACHEII scores, providing up to 80% of added prognostic value. In conclusion, time trends of MR-proADM may provide additional insights for patient risk stratification over single sampling. MR-proADM levels sampled both at presentation and after 72 h predicted 28-day survival in septic patients presenting to the ED. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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14 pages, 3033 KiB

Open AccessArticle

Increased Placental Anti-Oxidant Response in Asymptomatic and Symptomatic COVID-19 Third-Trimester Pregnancies

by Alessandro Rolfo, Stefano Cosma, Anna Maria Nuzzo, Chiara Salio, Laura Moretti, Marco Sassoè-Pognetto, Andrea Roberto Carosso, Fulvio Borella, Juan Carlos Cutrin and Chiara Benedetto

Biomedicines 2022, 10(3), 634; https://doi.org/10.3390/biomedicines10030634 - 09 Mar 2022

Cited by 4 | Viewed by 2313

Abstract

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae [...] Read more.

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women testing positive for SARS-CoV-2 during the third trimester of pregnancy showed redox-related alterations involving Catalase (CAT) and Superoxide Dismutase (SOD) antioxidant enzymes as well as placenta morphological anomalies relative to a cohort of healthy pregnant women. Next, we evaluated if placental redox-related alterations and mitochondria pathological changes were correlated with the presence of maternal symptoms. We observed ultrastructural alterations of placental mitochondria accompanied by increased levels of oxidative stress markers Thiobarbituric Acid Reactive Substances (TBARS) and Hypoxia Inducible Factor-1 α (HIF-1α) in SARS-CoV-2 women during the third trimester of pregnancy. Importantly, we found an increase in placental CAT and SOD antioxidant enzymes accompanied by physiological neonatal outcomes. Our findings strongly suggest a placenta-mediated OxS inhibition in response to SARS-CoV-2 infection, thus contrasting the cytotoxic profile caused by Coronavirus Disease 2019 (COVID-19). Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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16 pages, 1397 KiB

Open AccessArticle

The Role of Mid-Regional Proadrenomedullin in the Differential Diagnosis between Culture-Negative and Culture-Positive Sepsis at Emergency Department Admission

by Filippo Mearelli, Giulia Barbati, Francesca Spagnol, Alessio Nunnari, Luigi Mario Castello, Enrico Lupia, Maria Lorenza Muiesan, Salvatore Di Somma, Gian Carlo Avanzi and Gianni Biolo

Biomedicines 2022, 10(2), 357; https://doi.org/10.3390/biomedicines10020357 - 01 Feb 2022

Cited by 3 | Viewed by 1671

Abstract

Background: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated [...] Read more.

Background: The host response in culture-negative sepsis (CnS) has been marginally explored upon emergency department (ED) admission. It would be of paramount importance to create a clinical prediction rule to support the emergency department physician in identifying septic patients who can be treated with antibiotics immediately without waiting time to draw cultures if they are unlikely to provide useful diagnostic information. Methods: A multivariable logistic regression analysis was applied to identify the independent clinical variables and serum biomarkers of the culture-negative status among 773 undifferentiated septic patients. Those predictors were combined to build a nomogram predictive of CnS. Results: The serum concentrations of six biomarkers, among the eight biomarkers assayed in this study, were significantly lower in the patients with CnS (449) than in those with culture-positive sepsis (324). After correction for co-variates, only mid-regional proadrenomedullin (MR-proADM) was found to be independently correlated with culture-negative status. Absence of diabetes, hemoglobin concentrations, and respiratory source of infection were the other independent clinical variables integrated into the nomogram—its sensitivity and specificity for CnS were 0.80 and 0.79, respectively. Conclusions: Low concentrations of MR-proADM were independently associated with culture-negative sepsis. Our nomogram, based on the MR-proADM levels, did not predict culture-negative status with reasonable certainty in patients with a definitive diagnosis of sepsis at ED admission. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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11 pages, 976 KiB

Open AccessArticle

Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database

by Francesco Gavelli, Luca Molinari, Marco Baldrighi, Livia Salmi, Filippo Mearelli, Nicola Fiotti, Filippo Patrucco, Chiara Airoldi, Mattia Bellan, Pier Paolo Sainaghi, Salvatore Di Somma, Enrico Lupia, Efrem Colonetti, Maria Lorenza Muiesan, Gianni Biolo, Gian Carlo Avanzi and Luigi Mario Castello

Biomedicines 2022, 10(2), 198; https://doi.org/10.3390/biomedicines10020198 - 18 Jan 2022

Cited by 3 | Viewed by 1421

Abstract

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data [...] Read more.

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1–17.8] vs. 7.9 [3.8–12.9] ng/mL and 34.8 [26.4–47.5] vs. 29.8 [22.1–41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00–1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00–1.02] and 1.04 [1.02–1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00–1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02–1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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19 pages, 1679 KiB

Open AccessArticle

Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients

by Emanuel Moisa, Dan Corneci, Silvius Negoita, Cristina Raluca Filimon, Andreea Serbu, Mihai Ionut Negutu and Ioana Marina Grintescu

Biomedicines 2021, 9(11), 1656; https://doi.org/10.3390/biomedicines9111656 - 10 Nov 2021

Cited by 29 | Viewed by 2530

Abstract

Background: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). Objectives: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic [...] Read more.

Background: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). Objectives: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. Methods: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. Results: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06–8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21–5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7–4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31–3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2–2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13–2.49, p = 0.01). Conclusions: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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12 pages, 1246 KiB

Open AccessCommunication

Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

by Tommaso Tonetti, Giacomo Grasselli, Paola Rucci, Francesco Alessandri, Alessio Dell’Olio, Annalisa Boscolo, Laura Pasin, Nicolò Sella, Chiara Mega, Rita Maria Melotti, Massimo Girardis, Stefano Busani, Giacomo Bellani, Giuseppe Foti, Domenico Luca Grieco, Vittorio Scaravilli, Alessandro Protti, Thomas Langer, Luciana Mascia, Francesco Pugliese, Maurizio Cecconi, Roberto Fumagalli, Stefano Nava, Massimo Antonelli, Arthur S. Slutsky, Paolo Navalesi, Antonio Pesenti and Vito Marco Ranieri Show full author list Hide full author list

Biomedicines 2021, 9(9), 1228; https://doi.org/10.3390/biomedicines9091228 - 15 Sep 2021

Cited by 9 | Viewed by 2400

Abstract

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance [...] Read more.

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO₂/FiO₂ ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH₂O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH₂O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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Review

Jump to: Research

18 pages, 1880 KiB

Open AccessReview

Insight on Infections in Diabetic Setting

by Bianca Pari, Matteo Gallucci, Alberto Ghigo and Maria Felice Brizzi

Biomedicines 2023, 11(3), 971; https://doi.org/10.3390/biomedicines11030971 - 21 Mar 2023

Cited by 2 | Viewed by 1812

Abstract

The correlation between diabetes mellitus and infectious diseases is widely recognized. DM patients are characterized by the impaired function of the immune system. This translates into the occurrence of a variety of infections, including urinary tract, skin and surgical site infections, pneumonia, tuberculosis, [...] Read more.

The correlation between diabetes mellitus and infectious diseases is widely recognized. DM patients are characterized by the impaired function of the immune system. This translates into the occurrence of a variety of infections, including urinary tract, skin and surgical site infections, pneumonia, tuberculosis, and, more recently, SARS-CoV-2. Hyperglycemia has been identified as a relevant factor contributing to unfavorable outcomes in hospitalized patients including SARS-CoV-2 patients. Several studies have been performed proving that to maintain the proper and stringent monitoring of glycemia, a balanced diet and physical activity is mandatory to reduce the risk of infections and their associated complications. This review is focused on the mechanisms accounting for the increased susceptibility of DM patients to infections, with particular attention to the impact of newly introduced hypoglycemic drugs in sepsis management. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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13 pages, 674 KiB

Open AccessReview

Pathogenesis of Vascular Retinal Manifestations in COVID-19 Patients: A Review

by Elisa D’Alessandro, Aki Kawasaki and Chiara M. Eandi

Biomedicines 2022, 10(11), 2710; https://doi.org/10.3390/biomedicines10112710 - 26 Oct 2022

Cited by 10 | Viewed by 1359

Abstract

Pandemic infection secondary to coronavirus disease 2019 (COVID-19) had an important impact on the general population affecting not only respiratory tract but also many other organs. Ocular manifestations are quite common at the level of the anterior segment (conjunctivitis, dry eye), [...] Read more.

Pandemic infection secondary to coronavirus disease 2019 (COVID-19) had an important impact on the general population affecting not only respiratory tract but also many other organs. Ocular manifestations are quite common at the level of the anterior segment (conjunctivitis, dry eye), while posterior segment and, in particular, retinal findings are less frequent. In the retina, COVID-19 is associated with vascular events. Since retinal arteries and veins represent an accessible window to the microvasculature of the rest of the body, a better understanding of the profile of retinal vascular occlusive events may help elucidate mechanisms of thrombo-occlusive complications in other organs in patients affected by COVID-19. In this review, we conducted a systematic literature search focused on retinal arterial and/or retinal venous manifestations. Twenty-one studies were included, describing a wide range of manifestations from mild signs like cotton wool spots, focal and flame-shaped hemorrhages, and vein dilation to more severe retinal artery and vein occlusions. Two principal pathogenetic mechanisms are considered responsible for these complications: a hypercoagulative state and a massive inflammatory response leading to a disseminated intravascular coagulation-like syndrome. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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20 pages, 853 KiB

Open AccessReview

Biological and Exploitable Crossroads for the Immune Response in Cancer and COVID-19

by Letizia Vitali, Alessandra Merlini, Federica Galvagno, Alessia Proment and Dario Sangiolo

Biomedicines 2022, 10(10), 2628; https://doi.org/10.3390/biomedicines10102628 - 19 Oct 2022

Cited by 1 | Viewed by 1593

Abstract

The outbreak of novel coronavirus disease 2019 (COVID-19) has exacted a disproportionate toll on cancer patients. The effects of anticancer treatments and cancer patients’ characteristics shared significant responsibilities for this dismal outcome; however, the underlying immunopathological mechanisms are far from being completely understood. [...] Read more.

The outbreak of novel coronavirus disease 2019 (COVID-19) has exacted a disproportionate toll on cancer patients. The effects of anticancer treatments and cancer patients’ characteristics shared significant responsibilities for this dismal outcome; however, the underlying immunopathological mechanisms are far from being completely understood. Indeed, despite their different etiologies, SARS-CoV-2 infection and cancer unexpectedly share relevant immunobiological connections. In the pathogenesis and natural history of both conditions, there emerges the centrality of the immune response, orchestrating the timed appearance, functional and dysfunctional roles of multiple effectors in acute and chronic phases. A significant number (more than 600) of observational and interventional studies have explored the interconnections between COVID-19 and cancer, focusing on aspects as diverse as psychological implications and prognostic factors, with more than 4000 manuscripts published so far. In this review, we reported and discussed the dynamic behavior of the main cytokines and immune system signaling pathways involved in acute vs. early, and chronic vs. advanced stages of SARS-CoV-2 infection and cancer. We highlighted the biological similarities and active connections within these dynamic disease scenarios, exploring and speculating on possible therapeutic crossroads from one setting to the other. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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27 pages, 1168 KiB

Open AccessReview

Dual Role of Extracellular Vesicles in Sepsis-Associated Kidney and Lung Injury

by Marco Quaglia, Vito Fanelli, Guido Merlotti, Andrea Costamagna, Maria Chiara Deregibus, Marita Marengo, Eleonora Balzani, Luca Brazzi, Giovanni Camussi and Vincenzo Cantaluppi

Biomedicines 2022, 10(10), 2448; https://doi.org/10.3390/biomedicines10102448 - 30 Sep 2022

Cited by 2 | Viewed by 2634

Abstract

Extracellular vesicles form a complex intercellular communication network, shuttling a variety of proteins, lipids, and nucleic acids, including regulatory RNAs, such as microRNAs. Transfer of these molecules to target cells allows for the modulation of sets of genes and mediates multiple paracrine and [...] Read more.

Extracellular vesicles form a complex intercellular communication network, shuttling a variety of proteins, lipids, and nucleic acids, including regulatory RNAs, such as microRNAs. Transfer of these molecules to target cells allows for the modulation of sets of genes and mediates multiple paracrine and endocrine actions. EVs exert broad pro-inflammatory, pro-oxidant, and pro-apoptotic effects in sepsis, mediating microvascular dysfunction and multiple organ damage. This deleterious role is well documented in sepsis-associated acute kidney injury and acute respiratory distress syndrome. On the other hand, protective effects of stem cell-derived extracellular vesicles have been reported in experimental models of sepsis. Stem cell-derived extracellular vesicles recapitulate beneficial cytoprotective, regenerative, and immunomodulatory properties of parental cells and have shown therapeutic effects in experimental models of sepsis with kidney and lung involvement. Extracellular vesicles are also likely to play a role in deranged kidney-lung crosstalk, a hallmark of sepsis, and may be key to a better understanding of shared mechanisms underlying multiple organ dysfunction. In this review, we analyze the state-of-the-art knowledge on the dual role of EVs in sepsis-associated kidney/lung injury and repair. PubMed library was searched from inception to July 2022, using a combination of medical subject headings (MeSH) and keywords related to EVs, sepsis, acute kidney injury (AKI), acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Key findings are summarized into two sections on detrimental and beneficial mechanisms of actions of EVs in kidney and lung injury, respectively. The role of EVs in kidney-lung crosstalk is then outlined. Efforts to expand knowledge on EVs may pave the way to employ them as prognostic biomarkers or therapeutic targets to prevent or reduce organ damage in sepsis. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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15 pages, 1273 KiB

Open AccessReview

COVID-19, Endothelium and the Cardiometabolic Patient: A Possible Role for Capillary Leak Syndrome

by Vaia Lambadiari, Emmanouil Korakas, Evangelos Oikonomou, Evanthia Bletsa, Aikaterini Kountouri, Athina Goliopoulou, Ignatios Ikonomidis and Gerasimos Siasos

Biomedicines 2022, 10(10), 2379; https://doi.org/10.3390/biomedicines10102379 - 23 Sep 2022

Cited by 3 | Viewed by 1608

Abstract

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction [...] Read more.

Capillary leak syndrome is an under-diagnosed condition leading to serious hypoalbuminemia with diffuse edema, pulmonary edema, severe hypotension, and possibly death. Sepsis leading to hemophagocytic lymphohistiocytosis (HLH) is a major risk factor; however, capillary hyper-permeability is the core underlying pathophysiological mechanism. Endothelial dysfunction plays a major role in cardiometabolic disease through insulin resistance, lipotoxicity, and, eventually, oxidative stress and chronic inflammation. We review the literature concerning the aforementioned mechanisms as well-established risk factors for adverse COVID-19 outcomes. We especially focus on data regarding the underlying endothelial effects of SARS-CoV-2 infection, including direct damage and increased vascular leakage through a hyper-inflammatory cascade and diminished nitric oxide bioavailability. Interestingly, an increased incidence of hypoalbuminemia has been observed in patients with severe COVID-19, especially those with underlying cardiometabolic disease. Importantly, low albumin levels present a strong, positive association with poor disease outcomes. Therefore, in this review article, we highlight the important role of cardiovascular risk factors on endothelium integrity and the possible link of endothelial damage in the hypoalbuminemia-associated adverse prognosis of COVID-19 patients. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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13 pages, 537 KiB

Open AccessReview

The End of “One Size Fits All” Sepsis Therapies: Toward an Individualized Approach

by Jean-Louis Vincent, Tom van der Poll and John C. Marshall

Biomedicines 2022, 10(9), 2260; https://doi.org/10.3390/biomedicines10092260 - 12 Sep 2022

Cited by 17 | Viewed by 4401

Abstract

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection, remains a major challenge for clinicians and trialists. Despite decades of research and multiple randomized clinical trials, a specific therapeutic for sepsis is not available. The evaluation of [...] Read more.

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection, remains a major challenge for clinicians and trialists. Despite decades of research and multiple randomized clinical trials, a specific therapeutic for sepsis is not available. The evaluation of therapeutics targeting components of host response anomalies in patients with sepsis has been complicated by the inability to identify those in this very heterogeneous population who are more likely to benefit from a specific intervention. Additionally, multiple and diverse host response aberrations often co-exist in sepsis, and knowledge of which dysregulated biological organ system or pathway drives sepsis-induced pathology in an individual patient is limited, further complicating the development of effective therapies. Here, we discuss the drawbacks of previous attempts to develop sepsis therapeutics and delineate a future wherein interventions will be based on the host response profile of a patient. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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20 pages, 1148 KiB

Open AccessReview

Venous Thromboembolism in Sepsis: From Bench to Bedside

by Eleonora Galli, Elena Maggio and Fulvio Pomero

Biomedicines 2022, 10(7), 1651; https://doi.org/10.3390/biomedicines10071651 - 08 Jul 2022

Cited by 5 | Viewed by 3707

Abstract

Septic patients were commonly affected by coagulation disorders; thus, they are at high risk of thrombotic complications. In the last decades, novel knowledge has emerged about the interconnected and reciprocal influence of immune and coagulation systems. This phenomenon is called immunothrombosis, and it [...] Read more.

Septic patients were commonly affected by coagulation disorders; thus, they are at high risk of thrombotic complications. In the last decades, novel knowledge has emerged about the interconnected and reciprocal influence of immune and coagulation systems. This phenomenon is called immunothrombosis, and it indicates an effective response whereby immune cells and the coagulation cascade cooperate to limit pathogen invasion and endothelial damage. When this network becomes dysregulated due to a systemic inflammatory activation, as occurs during sepsis, it can result in pathological thrombosis. Endothelium, platelets and neutrophils are the main characters involved in this process, together with the TF and coagulation cascade, playing a critical role in both the host defense and in thrombogenesis. A deeper understanding of this relationship may allow us to answer the growing need for clinical instruments to establish the thrombotic risk and treatments that consider more the connection between coagulation and inflammation. Heparin remains the principal therapeutical response to this phenomenon, although not sufficiently effective. To date, no other significant alternatives have been found yet. In this review, we discuss the role of sepsis-related inflammation in the development and resolution of venous thromboembolism and its clinical implications, from bench to bedside. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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17 pages, 764 KiB

Open AccessReview

Bacterial and Viral Infections in Liver Transplantation: New Insights from Clinical and Surgical Perspectives

by Nour Shbaklo, Francesco Tandoi, Tommaso Lupia, Silvia Corcione, Renato Romagnoli and Francesco Giuseppe De Rosa

Biomedicines 2022, 10(7), 1561; https://doi.org/10.3390/biomedicines10071561 - 30 Jun 2022

Cited by 6 | Viewed by 4327

Abstract

End-stage liver disease patients undergoing liver transplantation are prone to develop numerous infectious complications because of immunosuppression, surgical interventions, and malnutrition. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80%. The challenges faced [...] Read more.

End-stage liver disease patients undergoing liver transplantation are prone to develop numerous infectious complications because of immunosuppression, surgical interventions, and malnutrition. Infections in transplant recipients account for the main cause of mortality and morbidity with rates of up to 80%. The challenges faced in the early post-transplant period tend to be linked to transplant procedures and nosocomial infections commonly in bloodstream, surgical, and intra-abdominal sites. Viral infections represent an additional complication of immunosuppression; they can be donor-derived, reactivated from a latent virus, nosocomial or community-acquired. Bacterial and viral infections in solid organ transplantation are managed by prophylaxis, multi-drug resistant screening, risk assessment, vaccination, infection control and antimicrobial stewardship. The aim of this review was to discuss the epidemiology of bacterial and viral infections in liver transplants, infection control issues, as well as surgical frontiers of ex situ liver perfusion. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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16 pages, 4168 KiB

Open AccessReview

High Doses of Inhaled Nitric Oxide as an Innovative Antimicrobial Strategy for Lung Infections

by Lorenzo Del Sorbo, Vinicius S. Michaelsen, Aadil Ali, Aizhou Wang, Rafaela V. P. Ribeiro and Marcelo Cypel

Biomedicines 2022, 10(7), 1525; https://doi.org/10.3390/biomedicines10071525 - 28 Jun 2022

Cited by 7 | Viewed by 3890

Abstract

Since the designation of nitric oxide as “Molecule of the Year” in 1992, the scientific and clinical discoveries concerning this biomolecule have been greatly expanding. Currently, therapies enhancing the release of endogenous nitric oxide or the direct delivery of the exogenous compound are [...] Read more.

Since the designation of nitric oxide as “Molecule of the Year” in 1992, the scientific and clinical discoveries concerning this biomolecule have been greatly expanding. Currently, therapies enhancing the release of endogenous nitric oxide or the direct delivery of the exogenous compound are recognized as valuable pharmacological treatments in several disorders. In particular, the administration of inhaled nitric oxide is routinely used to treat patients with pulmonary hypertension or refractory hypoxemia. More recently, inhaled nitric oxide has been studied as a promising antimicrobial treatment strategy against a range of pathogens, including resistant bacterial and fungal infections of the respiratory system. Pre-clinical and clinical findings have demonstrated that, at doses greater than 160 ppm, nitric oxide has antimicrobial properties and can be used to kill a broad range of infectious microorganisms. This review focused on the mechanism of action and current evidence from in vitro studies, animal models and human clinical trials of inhaled high-dose nitric oxide as an innovative antimicrobial therapy for lung infections. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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24 pages, 982 KiB

Open AccessReview

Unbalanced IDO1/IDO2 Endothelial Expression and Skewed Keynurenine Pathway in the Pathogenesis of COVID-19 and Post-COVID-19 Pneumonia

by Marco Chilosi, Claudio Doglioni, Claudia Ravaglia, Guido Martignoni, Gian Luca Salvagno, Giovanni Pizzolo, Vincenzo Bronte and Venerino Poletti

Biomedicines 2022, 10(6), 1332; https://doi.org/10.3390/biomedicines10061332 - 06 Jun 2022

Cited by 8 | Viewed by 3508

Abstract

Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this [...] Read more.

Despite intense investigation, the pathogenesis of COVID-19 and the newly defined long COVID-19 syndrome are not fully understood. Increasing evidence has been provided of metabolic alterations characterizing this group of disorders, with particular relevance of an activated tryptophan/kynurenine pathway as described in this review. Recent histological studies have documented that, in COVID-19 patients, indoleamine 2,3-dioxygenase (IDO) enzymes are differentially expressed in the pulmonary blood vessels, i.e., IDO1 prevails in early/mild pneumonia and in lung tissues from patients suffering from long COVID-19, whereas IDO2 is predominant in severe/fatal cases. We hypothesize that IDO1 is necessary for a correct control of the vascular tone of pulmonary vessels, and its deficiency in COVID-19 might be related to the syndrome’s evolution toward vascular dysfunction. The complexity of this scenario is discussed in light of possible therapeutic manipulations of the tryptophan/kynurenine pathway in COVID-19 and post-acute COVID-19 syndromes. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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14 pages, 292 KiB

Open AccessReview

COVID-19 and Lung Cancer: A Comprehensive Overview from Outbreak to Recovery

by Maristella Bungaro, Francesco Passiglia and Giorgio V. Scagliotti

Biomedicines 2022, 10(4), 776; https://doi.org/10.3390/biomedicines10040776 - 26 Mar 2022

Cited by 7 | Viewed by 2226

Abstract

Lung cancer patients have been associated with an increased risk of COVID-19 infection, pulmonary complications, and worse survival outcomes compared to the general population. The world’s leading professional organizations provided new recommendations for the diagnosis, treatment, and follow-up of lung cancer patients during [...] Read more.

Lung cancer patients have been associated with an increased risk of COVID-19 infection, pulmonary complications, and worse survival outcomes compared to the general population. The world’s leading professional organizations provided new recommendations for the diagnosis, treatment, and follow-up of lung cancer patients during the pandemic as a guide for prioritizing cancer care issues. Telemedicine was preferred for non-urgent consultations, and screening programs were temporarily suspended, leading to possible diagnostic delays along with an estimated increase in cause-specific mortality. A vaccine campaign has recently emerged as the main weapon to fight the COVID-19 pandemic, inverting this negative trend. This work aims to provide a comprehensive overview of the epidemiology and immune-pathophysiology of SARS-CoV-2 infection in cancer patients, highlighting the most relevant changes in the clinical management of lung cancer patients during the pandemic. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

43 pages, 1553 KiB

Open AccessReview

The Impact of SARS-CoV-2 Infection on Youth Mental Health: A Narrative Review

by Claudio Brasso, Silvio Bellino, Cecilia Blua, Paola Bozzatello and Paola Rocca

Biomedicines 2022, 10(4), 772; https://doi.org/10.3390/biomedicines10040772 - 25 Mar 2022

Cited by 22 | Viewed by 3727

Abstract

Background: COVID-19 pandemic has affected the physical health, psychological wellbeing, and mental health of the whole population. Young people are among those most at risk of developing mental health symptoms or disorders related to the pandemic. Purpose: the present narrative review is aimed [...] Read more.

Background: COVID-19 pandemic has affected the physical health, psychological wellbeing, and mental health of the whole population. Young people are among those most at risk of developing mental health symptoms or disorders related to the pandemic. Purpose: the present narrative review is aimed at providing an updated overview of the current literature concerning the psychological impact of the SARS-CoV-2 infection but also of the COVID-19 outbreak, environmental restriction, and social distancing on mental health outcomes among the youth population aged between 15 and 25 years. Methods: in December 2021, an electronic search on this topic was performed on PubMed. Relevant publications from January 2020 until December 2021 were included. Findings: 53 cross-sectional studies, 26 longitudinal studies, 4 ecological studies, 1 qualitative study, and 1 systematic review were included. We found many methodological limitations in the studies included, especially poor choice of study samples and short follow-ups. Little literature was in support of a strong relationship between SARS-CoV-2 infection and consequences on youth mental health. On the contrary, many studies showed how extraordinary measures to limit the spread of the virus have impacted young people in terms of onset of new mental disorders and symptoms, suicidality, and access to emergency psychiatric services. Depressive and anxiety symptoms and disorders show the greatest increase in incidence, especially in girls and young women. Conclusions: it seems important to pay attention to the mental health of young people in relation to the consequences of the COVID-19 pandemic. However, studies with more robust methodologies and longer follow-ups are needed to establish precise indications for targeted interventions in this context. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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10 pages, 519 KiB

Open AccessReview

PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury

by Jean Piero Margaria, Lucia Moretta, Jose Carlos Alves-Filho and Emilio Hirsch

Biomedicines 2022, 10(4), 756; https://doi.org/10.3390/biomedicines10040756 - 23 Mar 2022

Cited by 21 | Viewed by 2963

Abstract

Pulmonary fibrosis is a pathological fibrotic process affecting the lungs of five million people worldwide. The incidence rate will increase even more in the next years due to the long-COVID-19 syndrome, but a resolving treatment is not available yet and usually prognosis is [...] Read more.

Pulmonary fibrosis is a pathological fibrotic process affecting the lungs of five million people worldwide. The incidence rate will increase even more in the next years due to the long-COVID-19 syndrome, but a resolving treatment is not available yet and usually prognosis is poor. The emerging role of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling in fibrotic processes has inspired the testing of drugs targeting the PI3K/Akt pathway that are currently under clinical evaluation. This review highlights the progress in understanding the role of PI3K/Akt in the development of lung fibrosis and its causative pathological context, including sepsis as well as acute lung injury (ALI) and its consequent acute respiratory distress syndrome (ARDS). We further summarize current knowledge about PI3K inhibitors for pulmonary fibrosis treatment, including drugs under development as well as in clinical trials. We finally discuss how the design of inhaled compounds targeting the PI3K pathways might potentiate efficacy and improve tolerability. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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19 pages, 819 KiB

Open AccessReview

Bacterial and Viral Infection and Sepsis in Kidney Transplanted Patients

by Alberto Mella, Filippo Mariano, Caterina Dolla, Ester Gallo, Ana Maria Manzione, Maria Cristina Di Vico, Rossana Cavallo, Francesco Giuseppe De Rosa, Cristina Costa and Luigi Biancone

Biomedicines 2022, 10(3), 701; https://doi.org/10.3390/biomedicines10030701 - 18 Mar 2022

Cited by 8 | Viewed by 3334

Abstract

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree [...] Read more.

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree of immunosuppression, time after transplantation, type of infection, and patient conditions. Prevention, early diagnosis, and appropriate therapy are the goals of infective management, taking into account that some specific characteristics of transplanted patients may cause a delay (the absence of fever or inflammatory symptoms, the negativity of serological tests commonly adopted for the general population, or the atypical anatomical presentation depending on the surgical site and graft implantation). This review considers the recent available findings of the most common viral and bacterial infection in kidney transplanted patients and explores risk factors and outcomes in septic evolution. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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18 pages, 384 KiB

Open AccessReview

Therapy of Chronic Viral Hepatitis: The Light at the End of the Tunnel?

by Giorgio Maria Saracco, Alfredo Marzano and Mario Rizzetto

Biomedicines 2022, 10(3), 534; https://doi.org/10.3390/biomedicines10030534 - 24 Feb 2022

Cited by 4 | Viewed by 2568

Abstract

Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of [...] Read more.

Chronic viral hepatitis determines significant morbidity and mortality globally and is caused by three main etiological actors (Hepatitis B Virus, Hepatitis C Virus, and Hepatitis D Virus) with different replicative cycles and biological behaviors. Thus, therapies change according to the different characteristics of the viruses. In chronic hepatitis B, long term suppressive treatments with nucleoside/nucleotide analogues have had a dramatic impact on the evolution of liver disease and liver-related complications. However, a conclusive clearance of the virus is difficult to obtain; new strategies that are able to eradicate the infection are currently objects of research. The therapy for Hepatitis D Virus infection is challenging due to the unique virology of the virus, which uses the synthetic machinery of the infected hepatocyte for its own replication and cannot be targeted by conventional antivirals that are active against virus-coded proteins. Recently introduced antivirals, such as bulevertide and lonafarnib, display definite but only partial efficacy in reducing serum HDV-RNA. However, in combination with pegylated interferon, they provide a synergistic therapeutic effect and appear to represent the current best therapy for HDV-positive patients. With the advent of Direct Acting Antiviral Agents (DAAs), a dramatic breakthrough has occurred in the therapeutic scenario of chronic hepatitis C. Cure of HCV infection is achieved in more than 95% of treated patients, irrespective of their baseline liver fibrosis status. Potentially, the goal of global HCV elimination by 2030 as endorsed by the World Health Organization can be obtained if more global subsidised supplies of DAAs are provided. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

11 pages, 6033 KiB

Open AccessReview

Neuropsychological Outcome of Critically Ill Patients with Severe Infection

by Maria Della Giovampaola, Irene Cavalli and Luciana Mascia

Biomedicines 2022, 10(3), 526; https://doi.org/10.3390/biomedicines10030526 - 23 Feb 2022

Cited by 7 | Viewed by 2388

Abstract

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to [...] Read more.

Sepsis and septic shock represent important burdens of disease around the world. Sepsis-associated neurological consequences have a great impact on patients, both in the acute phase and in the long term. Sepsis-associated encephalopathy (SAE) is a severe brain dysfunction that may contribute to long-term cognitive impairment. Its pathophysiology recognizes the following two main mechanisms: neuroinflammation and hemodynamic impairment. Clinical manifestations include different forms of altered mental status, from agitation and restlessness to delirium and deep coma. A definite diagnosis is difficult because of the absence of specific radiological and biological criteria; clinical management is restricted to the treatment of sepsis, focusing on early detection of the infection source, maintenance of hemodynamic homeostasis, and avoidance of metabolic disturbances or neurotoxic drugs. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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26 pages, 1480 KiB

Open AccessReview

Novel Insight into the Mechanisms of the Bidirectional Relationship between Diabetes and Periodontitis

by Federica Barutta, Stefania Bellini, Marilena Durazzo and Gabriella Gruden

Biomedicines 2022, 10(1), 178; https://doi.org/10.3390/biomedicines10010178 - 16 Jan 2022

Cited by 23 | Viewed by 6786

Abstract

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated [...] Read more.

Periodontitis and diabetes are two major global health problems despite their prevalence being significantly underreported and underestimated. Both epidemiological and intervention studies show a bidirectional relationship between periodontitis and diabetes. The hypothesis of a potential causal link between the two diseases is corroborated by recent studies in experimental animals that identified mechanisms whereby periodontitis and diabetes can adversely affect each other. Herein, we will review clinical data on the existence of a two-way relationship between periodontitis and diabetes and discuss possible mechanistic interactions in both directions, focusing in particular on new data highlighting the importance of the host response. Moreover, we will address the hypothesis that trained immunity may represent the unifying mechanism explaining the intertwined association between diabetes and periodontitis. Achieving a better mechanistic insight on clustering of infectious, inflammatory, and metabolic diseases may provide new therapeutic options to reduce the risk of diabetes and diabetes-associated comorbidities. Full article

(This article belongs to the Special Issue Bacterial and Viral Infection and Sepsis: From Pathogenesis to Therapeutic Strategies)

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