Heart transplantation without informed consent: discussion of a case

OBJECTIVE: To discuss informed consent to heart transplantation in the case of an intensive care unit (ICU) patient: relatives' informed consent was refused by the patient himself whose cognitive ability appeared to be reasonable for the purpose. SETTING: ICU of a university teaching hospital. PATIENT: A 62-year-old man who underwent myocardial revascularization had in the immediate post-operative hemodynamic instability, continuous serious arrhythmias, ventilatory support, fentanyl infusion. Heart transplantation could be the only chance for his survival. INVENTION: Heart transplantation. RESULTS: Despite patient's refusal, we decided to hold the relative's consent as valid, and transplantation was accordingly performed, to the subsequent satisfaction of the patient. CONCLUSIONS: Our decision was based on two beliefs: (1) the severity of the patient's clinical condition may have impaired his cognitive abilities; (2) the very same conditions may mask impairment and certainly make reliable assessment of cognition and judgment impossible. This being so, the preservation of life assumes priority

Real-Time TDM-Based Expert Clinical Pharmacological Advice Program for Attaining Aggressive Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Meropenem in the Treatment of Critically Ill Patients with Documented Gram-Negative Infections Undergoing Continuous Veno-Venous Hemodiafiltration

: (1) Objectives: to describe the pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) meropenem in critical patients with documented Gram-negative infections undergoing continuous veno-venous hemodiafiltration (CVVHDF) and to assess the relationship with microbiological outcome. (2) Methods: Data were retrospectively retrieved for patients admitted to the general and the post-transplant intensive care units in the period October 2022-May 2023 who underwent CVVHDF during treatment with CI meropenem optimized by means of a real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) program for documented Gram-negative infections. Steady-state meropenem plasma concentrations were measured, and the free fractions (fCss) were calculated. Meropenem total clearance (CLtot) was calculated at each TDM assessment, and the impact of CVVHDF dose intensity and of residual diuresis on CLtot was investigated by means of linear regression. Optimal meropenem PK/PD target attainment was defined as an fCss/MIC ratio > 4. The relationship between meropenem PK/PD target attainment and microbiological outcome was assessed. (3) Results: A total of 24 critical patients (median age 68 years; male 62.5%) with documented Gram-negative infections were included. Median (IQR) meropenem fCss was 19.9 mg/L (17.4-28.0 mg/L). Median (IQR) CLtot was 3.89 L/h (3.28-5.29 L/h), and median (IQR) CVVHDF dose intensity was 37.4 mL/kg/h (33.8-44.6 mL/kg/h). Meropenem dosing adjustments were provided in 20 out of 24 first TDM assessments (83.3%, all decreases) and overall in 26 out of the 51 total ECPA cases (51.0%). Meropenem PK/PD target attainment was always optimal, and microbiological eradication was achieved in 90.5% of assessable cases. (4) Conclusion: the real-time TDM-guided ECPA program was useful in attaining aggressive PK/PD targeting with CI meropenem in critically ill patients undergoing high-intensity CVVHDF and allowed microbiological eradication in most cases with dosing regimens ranging between 125 and 500 mg q6h over 6 h

Comprehensive analysis and configuration of a control loading solution for a rotary wing flight simulator

This paper introduces a tilt-rotor flight simulation platform for research and teaching purposes implementing a real-time simulation of the Bell XV-15 aircraft. The mathematical model of the XV-15 aircraft has been implemented including simplified models for the aerodynamics of the whole aircraft, rotors, and engine dynamics. Hence, the simulation is performed in a graphic environment to reproduce the simulated flight and to interact with it using commands given by the pilot. The simulation platform is implemented using MATLAB/Simulink®, while the input commands are set using USB peripherals, i.e., a flight stick and a pedal board. Instead, the visualization environment is performed using FlightGear, an open-source and cross-platform software that is widely used in research. The result is a portable tilt-rotor simulator to be executed on a commercial pc, while ensuring real-time performance. The tilt-rotor flight simulator is also validated by a licensed helicopter pilot returning positive feedback regarding the flight experience

The Galaxy Starburst/Main-sequence Bimodality over Five Decades in Stellar Mass at z ≈ 3–6.5

We study the relation between stellar mass (M*) and star formation rate (SFR) for star-forming galaxies over approximately five decades in stellar mass (5.5 <~ log10(M*/Msun) <~ 10.5) at z ~ 3-6.5. This unprecedented coverage has been possible thanks to the joint analysis of blank non-lensed fields (COSMOS/SMUVS) and cluster lensing fields (Hubble Frontier Fields) which allow us to reach very low stellar masses. Previous works have revealed the existence of a clear bimodality in the SFR-M* plane with a star-formation Main Sequence and a starburst cloud at z ~ 4-5. Here we show that this bimodality extends to all star-forming galaxies and is valid in the whole redshift range z ~ 3-6.5. We find that starbursts constitute at least 20% of all star-forming galaxies with M* >~ 10^9 Msun at these redshifts and reach a peak of 40% at z=4-5. More importantly, 60% to 90% of the total SFR budget at these redshifts is contained in starburst galaxies, indicating that the starburst mode of star-formation is dominant at high redshifts. Almost all the low stellar-mass starbursts with log10(M*/Msun) <~ 8.5 have ages comparable to the typical timescales of a starburst event, suggesting that these galaxies are being caught in the process of formation. Interestingly, galaxy formation models fail to predict the starburst/main-sequence bimodality and starbursts overall, suggesting that the starburst phenomenon may be driven by physical processes occurring at smaller scales than those probed by these models.Comment: 24 pages, including 15 figures (17 files in total) and 4 tables. The manuscript has been accepted for publication in the Ap

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

Objectives: The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization. Methods: Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir Cmin range was set at 1-3&nbsp;mg/L, and average ganciclovir trough concentrations (Cmin ) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average Cmin below or above 1 or 3&nbsp;mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir Cmin cut-off predictive for clinical efficacy or toxicity. Results: Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13&nbsp;159.75-151&nbsp;340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average Cmin below or above 1&nbsp;mg/L (100.0%&nbsp;vs. 53.8%; p&nbsp;= .25) and/or 3&nbsp;mg/L (65.2%&nbsp;vs. 33.3%; p = .20). ROC analysis did not allow to identify an average Cmin cut-off predictive of clinical efficacy or toxicity. Conclusions: No clear relationship between ganciclovir Cmin and neither CMV eradication nor safety issues was identified

The impact of preservation fluid culture on graft site arteritis: a systematic review and metanalysis

The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear

A new risk stratification score for the management of ultrasound‐detected B3 breast lesions

To develop a predictive scoring system for ultrasound-detected B3 lesions at ultrasound-guided core needle biopsy (US-CNB). A total of 2724 consecutive US-CNBs performed in our Institution (January 2011 to December 2014) were retrospectively reviewed. Inclusion criteria were as follows: (a) histopathological examination of the entire lesion or (b) availability of radiologic follow-up (FUP) ≥24 months. Patient- and lesion-related variables-patients' age, lesion consistency, lesion size, vascularization, BI-RADS category, and US-CNB result-were analyzed. Positive predictive values (PPVs) for malignancy were calculated correlating US-CNB results with excision histology or FUP. A scoring system for underlying malignancy was developed using risk factors weighting. A total of 102 B3 lesions were included: 27 atypical ductal hyperplasia (26.5%), 5 lobular intraepithelial neoplasia (4.9%), 32 radial scar (31.4%), 37 papillary lesions (36.3%), and 1 fibroepithelial lesion (0.9%). Surgery was performed on 71/102 (69.6%) lesions, and 22/71 were malignant; the remaining 31/102 lesions (30.4%) were unchanged at FUP. The overall PPV for malignancy was 21.6%. Patients' age (odds ratio [OR] = 3.63, P = 0.008), lesion consistency (OR = 5.96, P = 0.001), BI-RADS category (OR = 17.52, P < 0.001), and CNB result (OR = 3.6, P = 0.008) were associated with a higher risk of malignancy underestimation and selected as risk factors in the score definition. Two risk groups were identified: low (0-2 points) and high risk (3-5 points), with significantly different risk of malignancy underestimation (8.0% vs 59.3%, P < 0.001). The proposed score helps to predict the risk of malignancy underestimation and choose the management of B3 lesions at US-CNB

Flow mediated dilation in patient with Berlin Heart Incor left ventricle assist device

Endothelial function measured with brachial ultrasound (BU) is a validated prognostic factor in heart failure patients. LVAD (left ventricle assist device) application is a promising surgical technique to treat refractory heart failure patients both as a bridge to heart transplantation or as destination therapy. Clinical recovery in such patients may be associated to normal endothelial function measured by BU but, as recently reported, only in pulsatile flow LVAD patients. The present paper report a case of normal endothelial function even in a axial LVAD patient

Impact of a multidisciplinary management team on clinical outcome in ICU patients affected by Gram-negative bloodstream infections: a pre-post quasi-experimental study

Background: Bloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients' outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients. Methods: Pre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist. Results: Overall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58-75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p &lt; 0.001) and a decrease of overall antibiotic treatment (12 vs. 16 days, p &lt; 0.001). Despite no differences in delta SOFA and all-cause 30-day mortality, a significant decrease in microbiological failure (10.3% vs. 29.9%, p = 0.005) and a new-onset 30-day MDRO colonization (8.3% vs. 36.6%, p &lt; 0.001) in the post-phase was reported. At multivariable analysis adjusted for main covariates, the institution of a multidisciplinary management team (MMT) was found to be protective both for new MDRO colonization [OR 0.17, 95%CI(0.05-0.67)] and microbiological failure [OR 0.37, 95%CI (0.14-0.98)]. Conclusions: The institution of a MMT allowed for an optimization of antimicrobial treatments, reflecting to a significant decrease in new MDRO colonization and microbiological failure among critically ill patients

A retrospective multicentre study on dalbavancin effectiveness and cost-evaluation in sternotomic wound infection treatment: DALBA SWIT Study

To evaluate the cost-effectiveness of dalbavancin compared with standard of care (SoC) treatment as daptomycin or teicoplanin in patients with sternal wound infections (SWI)