Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Correction: Volume: 10 Issue: 1 Article Number: 44 DOI: 10.1186/s13601-020-00351-w Published: OCT 26 2020Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.Peer reviewe

Buffering capacity in sepsis: A prospective cohort study in critically ill patients

Background: The concept of buffering generally refers to the ability of a system/organism to withstand attempted changes. For acid-base balance in particular, it is the body’s ability to limit pH aberrations when factors that potentially affect it change. Buffering is vital for maintaining homeostasis of an organism. The present study was undertaken in order to investigate the probable buffering capacity changes in septic patients. Materials and methods: This prospective cohort study included 113 ICU patients (96 septic and 17 critically-ill non-septic/controls). The buffering capacity indices were assessed upon ICU admission and reassessed only in septic patients, either at improvement or upon severe deterioration. Applying Stewart’s approach, the buffering capacity was assessed with indices calculated from the observed central venous-arterial gradients: a) ΔPCO2/Δ[H+] or ΔpH, b) ΔSID/Δ[H+] or ΔpH. Results: In a generalized estimating equation linear regression model, septic patients displayed significant differences in ΔPCO2/ΔpH [beta coefficient = -47.63, 95% CI (-80.09) - (-15.17), p = 0.004], compared to non-septic patients on admission. Lower absolute value of ΔPCO2/ΔpH (%) on admission was associated with a significant reduction in ICU mortality (HR 0.98, 95% CI: 0.97-0.99, p = 0.02). At septic-group reassessment (remission or deterioration), one-unit increase of ΔPCO2/D[H+] reduced the ICU death hazard by 44% (HR 0.56, 95% CI: 0.33-0.96, p = 0.03). Conclusions: In the particular cohort of patients studied, a difference in the buffering capacity was recorded between septic and non-septic patients on admission. Moreover, buffering capacity was an independent predictor of fatal ICU outcome at both assessments, ICU-admission and sepsis remission or deterioration. © 2019, MDPI AG. All rights reserved

TACI Expression and Signaling in Chronic Lymphocytic Leukemia

TACI is a membrane receptor of BAFF and APRIL, contributing to the differentiation and survival of normal B cells. Although malignant B cells are also subjected on TACI signaling, there is a remarkable intradisease and interindividual variability of TACI expression in B-cell malignancies. The aim of our study was to explore the possible role of TACI signaling in the biology of chronic lymphocytic leukemia (CLL), including its phenotypic and clinical characteristics and prognosis. Ninety-four patients and 19 healthy controls were studied. CLL patients exhibited variable TACI expression, with the majority of cases displaying low to undetectable TACI, along with low to undetectable BAFF and increased APRIL serum levels compared to healthy controls. CLL cells with high TACI expression displayed a better survival capacity in vitro, when cultured with BAFF and/or APRIL. Moreover, TACI expression was positively correlated with the presence of monoclonal gammopathy and inversely with CD11c expression. Therefore, our study provides further evidence for the contribution of BAFF/APRIL signaling to CLL biology, suggesting also that TACI detection might be useful in the selection of patients for novel targeting therapeutic approaches

Older age, disease severity and co-morbidities independently predict mortality in critically ill patients with copd exacerbation

INTRODUCTION Mechanically ventilated critically ill patients with acute COPD exacerbation (AECOPD) have significantly higher rates of morbidity and mortality compared to patients hospitalized for AECOPD but not requiring ventilatory support. The aim of this study was to describe the characteristics and outcomes of ventilated critically ill AECOPD patients and to identify prognostic variables associated with 28-day ICU mortality. METHODS One hundred and twenty-seven patients admitted to the University respiratory ICU in ‘Sotiria’ Hospital due to AECOPD were retrospectively studied. Data were extracted from the medical records of the ICU database. Demographic features, comorbidities, disease severity, exacerbation rate, and treatment, were recorded along with SOFA and APACHE-II scores and laboratory variables. RESULTS Thirty-five percent of the patients died in the ICU (mean age 73±8 vs 67±8 years in survivors, p<0.001). Non-survivors had significantly more comorbidities compared to survivors (p<0.001), significantly higher APACHE II score (30±7 vs 22±7, p<0.001), and significantly higher rates of multi-organ failure (MOF) (62% vs 10.2%, p<0.001). Independent factors associated with ICU mortality were older age (OR=1.13 per year increase; 95% CI: 1.04–1.22, p=0.004), APACHE II score on admission (OR=1.11 per unit increase; 95% CI: 1.04–1.22, p=0.004), Charlson Comorbidity Index (CCI) (OR=1.79 per unit increase; 95% CI: 1.25–2.55, p=0.001), admission lactate levels (OR=2.60 per mEq/L increase; 95% CI: 1.17-5.80, p=0.019), and COPD severity (OR=4.57; 95% CI: 1.14–18.22, p=0.032). CONCLUSIONS Severe physiological derangement upon ICU admission, COPD disease severity and high co-morbidity burden are predictive factors of 28-day mortality in critically ill AECOPD patients. © 2021 Galani M. et al

Unfractionated heparin reduces hepcidin levels in critically ill patients

A strong anti-hepcidin activity has been observed in heparins. Mean hepcidin levels were significantly reduced compared to baseline, following the first day of unfractionated heparin administration in critically patients. Heparin displayed a strong independent negative association with hepcidin. These results may lead to future treatment methods of forms of anaemia characterised by hepcidin excess, common among the critically ill. © 2021 Royal Australasian College of Physician

Efficacy and safety of mometasone furoate vs nedocromil sodium as prophylactic treatment for moderate/severe seasonal allergic rhinitis

Background: The preventive use of medications has been proposed to be effective in the treatment of seasonal rhinitis. Objective: To evaluate the efficacy and safety of mometasone furoate and nedocromil sodium nasal sprays as prophylactic treatment for moderate to severe seasonal allergic rhinitis (SAR). Patients: Sixty-one patients were recruited from 3 referral allergy centers. Inclusion criteria were history of SAR for 2 years or longer, sensitization to relevant local pollen (grasses, Parietaria, and olive), and age older than 12 years. Methods: An open-label, randomized, parallel-group, "real-life" study design was used. Patients received mometasone furoate nasal spray once daily or nedocromil sodium nasal spray 3 times daily starting 2 to 4 weeks before the pollen season and continuing for up to 4 months. Instructions regarding the use of additional medications were given. Diary cards recording symptoms, use of medication, and adverse events were kept by the patients. Results: All 61 patients completed the study. The prophylactic use of mometasone furoate vs nedocromil sodium led to significantly more days without symptoms (75.1% vs 54.5%; P < .001). The mometasone furoate group also had lower nasal symptom scores (mean, 1.4 vs 2.9; median, 0 vs 2; P < .001) and was more satisfied (93.1% vs 43.5%; P < .001). No serious adverse event was recorded, and there was no difference between the treatments in any adverse event. Conclusions: Prophylactic administration of mometasone furoate before the pollen season is safe and may lead to improved control of SAR compared with the use of nedocromil sodium