Search

Background: In recent years, many aspects of the physiological role of PCSK9 have been elucidated, in particular regarding its role in lipid metabolism, cardiovascular risk but also its role in innate immunity. Increasing evidence is available on the involvement of PCSK9 in the pathogenesis of viral infections, mainly HCV, as well as in the regulation of host response to bacterial infections, mainly sepsis and septic shock. Moreover, the action of PCSK9 has been investigated as a crucial step in the pathogenesis of malaria infection and disease severity. Objective: Aim of this paper is to review available published literature on the role of PCSK9 in a wide array of infectious diseases. Conclusion: Besides the ongoing investigation on PCSK9 inhibition among HIV-infected patients for the treatment of HIV- and ART-related hyperlipidemia, preclinical studies indicate how PCSK9 is involved in reducing the replication of HCV. Moreover, a protective role of PCSK9 inhibition has also been proposed against dengue and SARS-CoV-2 viral infections. Interestingly, high plasmatic PCSK9 levels have been described in patients with sepsis. Finally, a loss of function in the PCSK9-encoding gene has been reported to possibly reduce mortality in malaria infection.

Maternal sepsis represents a leading cause of mortality and severe morbidity worldwide. In Italy, it is the second cause of direct maternal mortality. Delay in recognition and treatment initiation are the drivers of sepsis-associated adverse outcomes. Between November 2017 and October 2019, the Italian Obstetric Surveillance System coordinated a prospective population-based study on maternal sepsis occurring before or after childbirth from 22 weeks’ gestation onward and up to 42 days following the end of pregnancy. A nested 1:2 matched case-control study on postpartum sepsis was also performed. Maternal sepsis was diagnosed for the presence of suspected or confirmed infection alongside signs or symptoms of organ failure. The aim of this study was to assess maternal sepsis incidence and its associated risk factors, management, and perinatal outcomes. Six Italian regions, covering 48.2% of the national births, participated in the project. We identified an incidence rate of 5.5 per 10,000 maternities (95% CI 4.80–6.28). Seventy percent of patients had a low education level and one third were foreigners with a language barrier. Genital, respiratory, and urinary tract infections were the predominant sources of infection; the majority of cases was caused by E. coli and polymicrobial infections. The presence of vascular and indwelling bladder catheters was associated with a nine-fold increased risk of postpartum sepsis. There were no maternal deaths, but one fourth of women experienced a serious adverse event and 28.3% required intensive care; 1.8% of newborns died. Targeted interventions to increase awareness of maternal sepsis and its risk factors and management should be promoted.

To identify the characteristics of patients with sepsis or acute pyelonephritis (APN) combined with ureteral calculi and to analyze the risk factors in its causation. Methods: We included patients with sepsis or APN caused by ureteral calculi who received treatment in the United States from January 2003 to December 2017 using the Optum® deidentified Clinformatics® Datamart. Demographic factors and risk factors for the receipt of sepsis or APN were subsequently analyzed for statistical significance. Results: Of 467,502 urinary stone patients, age-matched multivariate analysis revealed that a history of urinary tract infection (OR 11.31, 95% CI 10.68–11.99, p < 0.0001) and female gender (OR 2.73, 95% CI 2.62–2.84, p < 0.0001) were significantly related to an increased risk of sepsis or APN. Conversely, a previous past medical history of urolithiasis (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) and cancer (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) were associated with a decreased risk of sepsis or APN. With regards to comorbidities, when more than one comorbidity was present, there was an additive effect with higher OR point estimates, rising to 11.31 (10.68–11.99) when three or more comorbidities present. History of urinary tract infection and female gender are risk factors for sepsis or APN in patients with ureteral calculi. Conclusions: This large national cohort reveals the characteristics of sepsis or APN combined with ureteral stone and provides an important baseline for the treatment of urolithiasis in the future.

Funder: Alma Mater Studiorum - Università di Bologna, Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications.

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p

Objective: Intra-abdominal septic complications (IASC) affect short-term outcomes after surgery for colon cancer. Blood transfusions have been associated with worse short-term results.The role of IASC and blood transfusions on long-term oncologic results is still debated. This study aims to assess the impact of these two variables on survival after curative colon cancer resection. Patients and methods: Retrospective analysis of a prospectively maintained database of patients who underwent curative surgery for colon cancer at a university hospital, between 1993 and 2010. Cox regression was used to identify the role of IASC and transfusions (alone and combined) on local recurrence (LR), disease-free survival (DES), and cancer-specific survival (CSS). Results: Out of the 1686 patients analyzed, 1277 fit in the inclusion criteria. Colorectal surgeons performed the procedure in 82.2% of the patients. Blood transfusions were administered to 25.8% of the patients. Thirty-day complication and mortality rates were 34.5% and 6.1%. IASC occurred in 9.9%. The mean follow-up was 66 months. The 5-year rates of LR, DES, and CSS were 7%, 79.8%, and 85.1%. The year of surgery and pT (Hazard ratio 9.35, 95% CI 1.23-70.9, for T4) and pN (Hazard ratio 2.57, 95% CI 1.39-4.72, for N2) stages were independent risk factors for LR. The same variables, bowel obstruction and surgeries performed by surgeons not specialized in colorectal surgery, were also associated with worse DES and CSS. IASC and blood transfusions were not associated with LR, DFS, and CSS, whether alone or combined. Conclusions: IASC and transfusions were not associated with worse oncological outcomes after curative colon cancer surgery per se. Other factors were more important predictors of survival. (C) 2019 Published by Elsevier Espana, S.L.U.

Deep neck space infections (DNSIs) are a group of infective suppurative diseases involving deep neck spaces and cervical fascia. Necrotising and septic evolutions are rare, but severe complications can dramatically affect the prognosis and should be promptly managed. Clinical examination often has low sensitivity, although instrumental diagnosis may delay te treatment. We investigated two laboratory tools, LRINEC (Laboratory Risk Indicator for the Necrotizing fasciitis) and NLR (neutrophil to lymphocyte ratio), in the expectation to find a rapidly available predictive indicator that may help in distinguishing necrotising complications and/or systemic septic involvement.A retrospective observational cohort study was performed on 118 patients who had underwent surgical treatment for DNSIs at our Surgical Unit. LRINEC, NLR and the product LRINEC x NLR were calculated.Statistical analysis showed that these scores may have utility in rapidly predicting the risk of necrotising fasciitis and systemic involvement at an early diagnostic stage.Further studies with a larger cohort may be necessary in order to increase the sensitivity and specificity.Nuovi indicatori biochimici predittivi di infezioni suppurative cervicali.Le infezioni suppurative del collo sono un eterogeneo gruppo di patologie a carico degli spazi profondi del collo e delle fasce cervicali. Al suo interno meritano particolare attenzione le temibili fasciti necrotizzanti, caratterizzate dall’elevato tasso di mortalità e di compromissione settica. Risulta pertanto indispensabile una loro pronta diagnosi e un altrettanto tempestivo trattamento. La semeiologia clinica risulta spesso poco sensibile, mentre l’esame TC comporta un inevitabile ritardo nella presa in carico terapeutica. Abbiamo quindi valutato l’applicabilità di due indicatori basati unicamente su parametri laboratoristici, quindi rapidamente disponibili: LRINEC score e NLR ratio.Abbiamo condotto uno studio retrospettivo su 118 pazienti che erano stati sottoposti a drenaggio chirurgico di ascesso cervicale c/o la nostra U.O., calcolando per ciascuno di essi LRINEC, NLR e il loro prodotto di moltiplicazione LRINEC x NLR.L’analisi statistica dimostra un loro possibile ruolo nella diagnosi tempestiva delle fasciti necrotizzanti e/o delle loro complicanze settiche.Ulteriori studi con una maggiore numerosità campionaria potrebbero essere necessari per rafforzare sensibilità e specificità di tali score.

Background: A prognostic stratification of mortality risk in older patients with sepsis admitted to medical wards is often challenging. Aims: To evaluate the ability of the Sequential Organ Failure Assessment (SOFA) score, serum biomarkers (lactate and C-Reactive Protein, CRP), and measures of comorbidity and frailty in predicting in-hospital and 6-month mortality in a cohort of older patients admitted to an Acute Geriatric Unit (AGU) with a diagnosis of sepsis. Methods: All patients aged 70 years and over consecutively admitted to our AGU with sepsis in the study period were included. At admission, a Comprehensive Geriatric Assessment including two measures of frailty (Clinical Frailty Scale [CFS], Frailty Index [FI]) was obtained. To assess the predictivity of candidate prognostic markers, the Area Under the Receiver-Operating Characteristic (AUROC) curves were analyzed. A multivariate logistic regression analysis was also performed. Results: We included 240 patients (median age = 85, IQR = 80–89, 40.8% women), of whom 33.8% died before discharge, and 60.4% at 6 months. The SOFA score (AUROC = 0.678, 95% CI 0.610–0.747) and CRP serum levels (AUROC = 0.606, 95% CI 0.532–0.680) were good predictors of in-hospital mortality. The CFS (AUROC = 0.703, 95% CI 0.637–0.768) and the FI (AUROC = 0.677, 95% CI 0.607–0.746) better predicted 6-month mortality. Results of the regression analysis confirmed the findings of the AUROC study. The combined assessment of SOFA and measures of frailty improved the performance of the model both in the short and the long term. Conclusions: Both the severity of organ dysfunction and frailty scores should be addressed on AGU admission to establish the short- and long-term outcomes of older patients with sepsis.

During gram-negative septicemia, interactions between platelets and neutrophils initiate a detrimental feedback loop that sustains neutrophil extracellular trap (NET) induction, disseminated intravascular coagulation, and inflammation. Understanding intracellular pathways that control platelet-neutrophil interactions is essential for identifying new therapeutic targets. Here, we found that thrombin signaling induced activation of the transcription factor NFAT in platelets. Using genetic and pharmacologic approaches, as well as iNFATuation, a newly developed mouse model in which NFAT activation can be abrogated in a cell-specific manner, we demonstrated that NFAT inhibition in activated murine and human platelets enhanced their activation and aggregation, as well as their interactions with neutrophils and NET induction. During gram-negative septicemia, NFAT inhibition in platelets promoted disease severity by increasing disseminated coagulation and NETosis. NFAT inhibition also partially restored coagulation ex vivo in patients with hypoactive platelets. Our results define non-transcriptional roles for NFAT that could be harnessed to address pressing clinical needs.

Introduction. Sepsis is an overwhelming reaction to infection with significant morbidity, requiring urgent interventions in order to improve outcomes. The 2016 Sepsis-3 guidelines modified the previous definitions of sepsis and septic shock, and proposed some specific diagnostic and therapeutic measures to define the use of fluid resuscitation and antibiotics. However, some open issues still exist. Methods. A literature research was performed on PubMed and Cochrane using the terms “sepsis” AND “intra-abdominal infections” AND (“antibiotic therapy” OR “antibiotic treatment”). The inclusion criteria were management of intra-abdominal infection (IAI) and effects of antibiotic stewardships programs (ASP) on the outcome of the patients. Discussion. Sepsis-3 definitions represent an added value in the understanding of sepsis mechanisms and in the management of the disease. However, some questions are still open, such as the need for an early identification of sepsis. Sepsis management in the context of IAI is particularly challenging and a prompt diagnosis is essential in order to perform a quick treatment (source control and antibiotic treatment). Antibiotic empirical therapy should be based on the kind of infection (community or hospital acquired), local resistances, and patient’s characteristic and comorbidities, and should be adjusted or de-escalated as soon as microbiological information is available. Antibiotic Stewardship Programs (ASP) have demonstrated to improve antimicrobial utilization with reduction of infections, emergence of multi-drug resistant bacteria, and costs. Surgeons should not be alone in the management of IAI but ideally inserted in a sepsis team together with anaesthesiologists, medical physicians, pharmacists, and infectious diseases specialists, meeting periodically to reassess the response to the treatment. Conclusion. The cornerstones of sepsis management are accurate diagnosis, early resuscitation, effective source control, and timely initiation of appropriate antimicrobial therapy. Current evidence shows that optimizing antibiotic use across surgical specialities is imperative to improve outcomes. Ideally every hospital and every emergency surgery department should aim to provide a sepsis team in order to manage IAI.

Objectives: To compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections. Data sources: MEDLINE, Google Scholar and the Cochrane Library.Study eligibility criteria and interventions: Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used as monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or hospital-acquired pneumonia/ventilator-associated pneumonia due to P. aeruginosa were included in this meta-analysis. The outcomes evaluated were in-hospital mortality rate, 14 -day-or 30-day-mortality rate, microbiological cure rate and clinical cure rate.Results: Of 8363 citations screened, six randomized controlled trials, six prospective cohort studies and 21 retrospective cohort studies were included in the analysis, accounting for a total of 3861 subjects. Considering the 14 studies evaluating empirical therapy, no significant difference in mortality rate was observed between the two groups [relative risk (RR) 1.06, 95% confidence interval (CI) 0.86-1.30; P = 0.6]. Similar findings were obtained among the 18 studies analysing targeted therapy (RR 1.04, 95% CI 0.83- 1.31; P = 0.708); however, grouping the studies by design, higher mortality was observed among patients receiving monotherapy in five prospective studies (RR 1.37, 95% CI 1.06-1.79; P = 0.018). Finally, no differ-ence was observed between groups in terms of microbiological cure and clinical cure.Conclusions: This meta-analysis demonstrated no difference in mortality rate, clinical cure rate and mi-crobiological cure rate in patients treated with beta-lactam monotherapy or combination therapy for P. aeruginosa infections.(c) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Summary Background Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms. Methods NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was −10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov ( NCT02790996 ). Findings Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference −7% [95% CI −15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group). Interpretation In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants. Funding EU Seventh Framework Programme for research, technological development and demonstration.

The Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to become a global pandemic, putting a strain on health care systems. SARS-CoV-2 infection may be associated with mild symptoms or, in severe cases, lead patients to the intensive care unit (ICU) or death. The critically ill patients suffer from acute respiratory distress syndrome (ARDS), sepsis, thrombotic complications and multiple organ failure. For optimization of hospital resources, several molecular markers and algorithms have been evaluated in order to stratify COVID-19 patients, based on the risk of developing a mild, moderate, or severe disease. Here, we propose the soluble urokinase receptor (suPAR) as a serum biomarker of clinical severity and outcome in patients who are hospitalized with COVID-19. In patients with mild disease course, suPAR levels were increased as compared to healthy controls, but they were dramatically higher in severely ill patients. Since early identification of disease progression may facilitate the individual management of COVID-19 symptomatic patients and the time of admission to the ICU, we suggest paying more clinical attention on patients with high suPAR levels.

Sepsis represents an important global health burden due to its high mortality and morbidity. The rapid detection of sepsis is crucial in order to prevent adverse outcomes and reduce mortality. However, the diagnosis of sepsis is still challenging and many efforts have been made to identify reliable biomarkers. Unfortunately, many investigated biomarkers have several limitations that do not support their introduction in clinical practice, such as moderate diagnostic and prognostic accuracy, long turn-around time, and high-costs. Complete blood count represents instead a precious test that provides a wealth of information on individual health status. It can guide clinicians to early-identify patients at high risk of developing sepsis and to predict adverse outcomes. It has several advantages, being cheap, easy-to-perform, and available in all wards, from the emergency department to the intensive care unit. Noteworthy, it represents a first-level test and an alteration of its parameters must always be considered within the clinical context, and the eventual suspect of sepsis must be confirmed by more specific investigations. In this review, we describe the usefulness of basic and new complete blood count parameters as diagnostic and prognostic biomarkers of sepsis.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 +/- 0.74. Sepsis (qSOFA >= 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 +/- 0.963) compared to upper-middle (0.17 +/- 0.482) and high-income (0.36 +/- 0.714) countries ( P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.

Background SARS-CoV-2 infection has spread worldwide, and the pathogenic mechanism is still under investigation. The presence of a huge inflammatory response, defined as “cytokine storm,” is being studied in order to understand what might be the prognostic factors implicated in the progression of the infection, with ferritin being one of such markers. The role of ferritin as a marker of inflammation is already known, and whether it changes differently between COVID and non-COVID patients still remains unclear. The aim of this retrospective analysis is to understand whether the inflammatory process in these two types is different. Methods In this retrospective analysis, we compared 17 patients affected by SARS-CoV-2, who had been admitted between February and April 2020 (group A) along with 30 patients admitted for acute surgical disease with SARS-CoV-2 negative swab (group B). A further subgroup of Covid negative patients with leukocytosis was compared to group A. Results In group A, the median (interquartile range) serum ferritin was 674 (1284) ng/mL, and it was double the cutoff (300 ng/mL) in 9 out of 17 (52%). The median (IQR) value of ferritin level in the total blood samples of group B was 231, and in the subgroup with leucocytosis, 149 (145). Group A showed a significantly higher ferritin median level compared to the entire group B (two-tailed Mann-Whitney test, p p Conclusions The role of iron metabolism appears to be directly involved in COVID infection. On the other hand, in the acute inflammation of patients admitted for surgery, and probably in other common phlogistic processes, iron modifications appear to be self-limited. However, our finding suggests the use of ferritin as a marker for COVID infection.

Purpose of review Despite its recognized efficacy and tolerability profile, during the last decade a rise of adverse events following ibuprofen administration in children has been reported, including a possible role in worsening the clinical course of infections. Our aim was to critically evaluate the safety of ibuprofen during the course of pediatric infectious disease in order to promote its appropriate use in children. Recent findings Ibuprofen is associated with severe necrotizing soft tissue infections (NSTI) during chickenpox course. Pre-hospital use of ibuprofen seems to increase the risk of complicated pneumonia in children. Conflicting data have been published in septic children, while ibuprofen in the setting of Cystic Fibrosis (CF) exacerbations is safe and efficacious. No data is yet available for ibuprofen use during COVID-19 course. Summary Ibuprofen should not be recommended for chickenpox management. Due to possible higher risks of complicated pneumonia, we suggest caution on its use in children with respiratory symptoms. While it remains unclear whether ibuprofen may have harmful effects during systemic bacterial infection, its administration is recommended in CF course. Despite the lack of data, it is seems cautious to prefer the use of paracetamol during COVID-19 acute respiratory distress syndrome in children.

The emergence of cell-based therapeutics, specifically the use of mesenchymal stromal/stem cells (MSCs), stands to significantly affect the future of targeted drug delivery technologies. MSCs represent a unique cell type, offering more than only regenerative potential but also site-specific inflammatory targeting and tissue infiltration. In this study, a versatile multicomponent delivery platform, combining MSC tropism with multistage nanovector (MSV)-mediated payload delivery, is debuted. It is demonstrated that the incorporation of drug-loaded MSVs bestows MSCs with the ability to transport anti-inflammatory payloads, achieving a fivefold increase in payload release without negatively impacting cellular functions, viability, extravasation, and inflammatory homing. When incorporated within MSCs, MSVs avoid rapid sequestration by filtering organs and conserve a 15-fold increase in local inflammatory targeting compared to healthy ears. Furthermore, this MSC-mediated MSV platform (M&Ms) rapidly triggers a 4.5-fold reduction of local inflammation compared to free drug and extends survival to 100% of treated mice in a lethal model of systemic inflammation.

Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a &beta, lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) aimed to evaluate the effectiveness of C/T combination therapy compared to C/T monotherapy for the treatment of severe infections and to describe the prevalence of microorganisms in the included studies. We retrieved literature from PubMed, EMBASE, and CENTRAL, until 26 November 2020. Eligible studies were both randomised trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was all-cause mortality, secondary outcomes were (i) clinical improvement and (ii) microbiological cure. Eight nonrandomised studies were included in the qualitative synthesis: Seven retrospective cohort studies and one case-control study. The meta-analysis of the four studies evaluating all-cause mortality (in total 148 patients: 87 patients treated with C/T alone and 61 patients treated with C/T combination therapy) showed a significant reduction of mortality in patients receiving C/T combination therapy, OR: 0.31, 95% CI: 0.10&ndash, 0.97, p = 0.045. Conversely, the meta-analysis of the studies evaluating clinical improvement and microbiological cure showed no differences in C/T combination therapy compared to C/T monotherapy. The most consistent data come from the analysis of the clinical improvement, n = 391 patients, OR: 0.97, 95% CI: 0.54&ndash, 1.74, p = 0.909. In 238 of the 391 patients included (60.8%), C/T was used for the treatment of infections caused by Pseudomonas aeruginosa.