Recruitment-to-inflation ratio reflects the impact of peep on dynamic lung strain in a highly recruitable model of ARDS.

BACKGROUND: The recruitment-to-inflation ratio (R/I) has been recently proposed to bedside assess response to PEEP. The impact of PEEP on ventilator-induced lung injury depends on the extent of dynamic strain reduction. We hypothesized that R/I may reflect the potential for lung recruitment (i.e. recruitability) and, consequently, estimate the impact of PEEP on dynamic lung strain, both assessed through computed tomography scan. METHODS: Fourteen lung-damaged pigs (lipopolysaccharide infusion) underwent ventilation at low (5 cmH2O) and high PEEP (i.e., PEEP generating a plateau pressure of 28-30 cmH2O). R/I was measured through a one-breath derecruitment maneuver from high to low PEEP. PEEP-induced changes in dynamic lung strain, difference in nonaerated lung tissue weight (tissue recruitment) and amount of gas entering previously nonaerated lung units (gas recruitment) were assessed through computed tomography scan. Tissue and gas recruitment were normalized to the weight and gas volume of previously ventilated lung areas at low PEEP (normalized-tissue recruitment and normalized-gas recruitment, respectively). RESULTS: Between high (median [interquartile range] 20 cmH2O [18-21]) and low PEEP, median R/I was 1.08 [0.88-1.82], indicating high lung recruitability. Compared to low PEEP, tissue and gas recruitment at high PEEP were 246 g [182-288] and 385 ml [318-668], respectively. R/I was linearly related to normalized-gas recruitment (r = 0.90; [95% CI 0.71 to 0.97) and normalized-tissue recruitment (r = 0.69; [95% CI 0.25 to 0.89]). Dynamic lung strain was 0.37 [0.29-0.44] at high PEEP and 0.59 [0.46-0.80] at low PEEP (p < 0.001). R/I was significantly related to PEEP-induced reduction in dynamic (r = - 0.93; [95% CI - 0.78 to - 0.98]) and global lung strain (r = - 0.57; [95% CI - 0.05 to - 0.84]). No correlation was found between R/I and and PEEP-induced changes in static lung strain (r = 0.34; [95% CI - 0.23 to 0.74]). CONCLUSIONS: In a highly recruitable ARDS model, R/I reflects the potential for lung recruitment and well estimates the extent of PEEP-induced reduction in dynamic lung strain.

Successful Benralizumab treatment in acute near-fatal asthma with ECMO support: a case report.

INTRODUCTION: Near-fatal asthma (NFA) is a severe condition that can lead to respiratory arrest or high carbon dioxide levels, often requiring mechanical ventilation. Biologics have revolutionized the management of severe asthma, significantly improving symptom severity, reducing the number of exacerbations and hospitalizations, and decreasing the need for oral corticosteroids. However, their effectiveness in acute settings, particularly for ICU patients experiencing severe respiratory failure, is not well-studied. More research is needed to determine if biologics can improve recovery during severe asthma exacerbations. CASE STUDY: We report a case of NFA in a patient with severe allergic eosinophilic asthma, who experienced global respiratory failure necessitating hospitalization, intubation, and veno-venous extracorporeal membrane oxygenation (VV-ECMO). Given the severity of the clinical condition, compassionate administration of Benralizumab, which targets the IL-5 receptor, was attempted. RESULTS: Five days from anti-IL5 receptor treatment start, the patient was extubated and the ECMO stopped. After the stepdown to the respiratory intensive care unit (RICU), the patient was weaned from oxygen therapy and subsequently discharged from hospital. CONCLUSION: Benralizumab demonstrated rapid effectiveness in improving respiratory failure leading to successful weaning from VV-ECMO and subsequent extubation.

Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: a Propensity Score Adjusted Retrospective Cohort Study.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy. METHODS: All consecutive patients with a GNB-BSI from January 1st, 2021, to April 1st, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed. RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset. CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.

Impact of positive end-expiratory pressure on renal resistive index in mechanical ventilated patients.

PURPOSE: Growing evidence shows the complex interaction between lung and kidney in critically ill patients. The renal resistive index (RRI) is a bedside measurement of the resistance of the renal blood flow and it is correlated with kidney injury. The positive end-expiratory pressure (PEEP) level could affect the resistance of renal blood flow, so we assumed that RRI could help to monitoring the changes in renal hemodynamics at different PEEP levels. Our hypothesis was that the RRI at ICU admission could predict the risk of acute kidney injury in mechanical ventilated critically ill patients. METHODS: We performed a prospective study including 92 patients requiring mechanical ventilation for ≥ 48 h. A RRI ≥ 0.70, was deemed as pathological. RRI was measured within 24 h from ICU admission while applying 5,10 and 15 cmH2O of PEEP in random order (PEEP trial). RESULTS: Overall, RRI increased from 0.62 ± 0.09 at PEEP 5 to 0.66 ± 0.09 at PEEP 15 (p < 0.001). The mean RRI value during the PEEP trial was able to predict the occurrence of AKI with AUROC = 0.834 [95%CI 0.742-0.927]. Patients exhibiting a RRI ≥ 0.70 were 17/92(18%) at PEEP 5, 28/92(30%) at PEEP 10, 38/92(41%) at PEEP 15, respectively. Thirty-eight patients (41%) exhibited RRI ≥ 0.70 at least once during the PEEP trial. In these patients, AKI occurred in 55% of the cases, versus 13% remaining patients, p < 0.001. CONCLUSIONS: RRI seems able to predict the risk of AKI in mechanical ventilated patients; further, RRI values are influenced by the PEEP level applied. TRIAL REGISTRATION: Clinical gov NCT03969914 Registered 31 May 2019.

Genotypic and phenotypic characteristics of Candida parapsilosis bloodstream isolates: Health Care Associated Infections in a teaching Hospital in Italy.

BACKGROUND: Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains. METHODS: From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates. RESULTS: A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates. CONCLUSION: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

Cryoglobulinemia: the "cold" problem in cardiac surgery, a single-center experience and a literature review.

Cardiac surgery with cardiopulmonary bypass (CBP) is essential for different cardiac procedures in order to perform surgery with a clear sight field.To safely perform surgery with CPB and preserve brain, kidney, and patient tissue from ischemic damage, cold cardioplegia, and mild to deep hypothermia are induced during the operation.Cryoglobulinemia is a hematological/infective-related disease (in certain cases idiopathic) in which temperature-dependent antibodies tend to aggregate and form emboli in the vascular system causing tissue damage if exposed to low temperature.The patient with cryoglobulinemia (known and unknown) can be at risk of a major ischemic event during CPB and induced hypothermia.This article's aim is to evaluate the present scientific literature in order to understand how, in years, the therapeutic or preventive approach, is evolving, and to analyze and make improvements to the management of a cryoglobulinemic patient who must undergo elective or emergency cardiac surgery.In the last part of our article, we expose our single-center experience during a 32-month-long period of survey.In all cases, our medical team (anesthesiologists, perfusionists, and cardiac surgeons) opted for a normothermic cardiopulmonary bypass to lower the risk of cryoglobulin-associated complications.In our experience, along with therapeutic intervention to lower the cryoglobulin titer, normothermic management of cardiopulmonary bypass is as safe as hypothermic management.Notwithstanding our results, further studies with a larger population are needed to confirm this perioperative management in a cardiac surgery setting.

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

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

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock.

BACKGROUND: According to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain "subclinical" during early resuscitation. We hypothesized that "subclinical" cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min-1. RESULTS: At ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min-1 vs 6.6 ± 1.9 min-1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm-5/m2, p < 0.01). CONCLUSIONS: In patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.

Cefiderocol Versus Colistin for the Treatment of Carbapenem-Resistant Acinetobacter baumannii Complex Bloodstream Infections: A Retrospective, Propensity-Score Adjusted, Monocentric Cohort Study.

INTRODUCTION: Bloodstream infections (BSI) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with high mortality with limited treatment. The aim of this study is to compare effectiveness and safety of colistin-based versus cefiderocol-based therapies for CRAB-BSI. METHODS: This is a retrospective observational study enrolling patients with monomicrobial CRAB-BSIs treated with colistin or cefiderocol from 1 January 2020, to 31 December 2022. The 30-day all-cause mortality rate was the primary outcome. A Cox regression analysis was performed to identify factors independently associated with mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. RESULTS: Overall 118 patients were enrolled, 75 (63%) and 43 (37%) treated with colistin- and cefiderocol-based regimens. The median (q1-q3) age was 70 (62-79) years; 70 (59%) patients were men. The 30-day all-cause mortality was 52%, significantly lower in the cefiderocol group (40% vs 59%, p = 0.045). By performing a Cox regression model, age (aHR = 1.03, 95% CI 1.00-1.05), septic shock (aHR = 1.93, 95% CI 1.05-3.53), and delayed targeted therapy (aHR = 2.42, 95% CI 1.11-5.25) were independent predictors of mortality, while cefiderocol-based therapy was protective (aHR = 0.49, 95% CI 0.25-0.93). The IPTW-adjusted Cox analysis confirmed the protective effect of cefiderocol (aHR = 0.53, 95% CI 0.27-0.98). CONCLUSIONS: Cefiderocol may be a valuable treatment option for CRAB-BSI, especially in the current context of limited treatment options.

Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study.

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar-arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F (r = - 0.389, p = 0.02) but directly to A-aDO2 (r = 0.699, p = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15+ cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3+, CD4+, CD8+, and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation.

Type 1 citrullinemia patient with Brugada pattern undergoing general anesthesia for dental extractions: A case report.

Key Clinical Message: The perioperative control of ammonia, reduction of stress, and administration of drugs tolerated in type 1 citrullinemia and Brugada pattern allowed the successful and uneventful management of general anesthesia in the study patient. Abstract: The aim of this study was to report the targeted perioperative management of general anesthesia (GA) adopted for dental extractions in a rare patient with type 1 citrullinemia and Brugada pattern. A male, Caucasian, adult type 1 citrullinemia patient needed dental extractions under GA. The medical history showed neurodevelopmental impairment, growth retardation, epilepsy, and a Type 2 Brugada electrocardiographic pattern in the second precordial lead. The authors focused the anesthesiologic protocol on the prevention of hyperammonemia and fatal arrhythmias. Changes in diet and 10% glucose solution administration prevented protein catabolism due to the fasting period (ammonia was 44 µmol/L preoperatively and 46 µmol/L postoperatively; glycemia was 120 g/dL preoperatively and 153 g/dL postoperatively). The patient received a continuous electrocardiogram, noninvasive blood pressure, pulse oximeter, entropy monitoring, train-of-four monitoring, and external biphasic defibrillator pads. Midazolam, remifentanil, and dexamethasone were administered for pre-anesthesia; thiopental and rocuronium for induction; remifentanil and desflurane for maintenance; sugammadex for decurarization. After the intraligamentary injection of lidocaine 2% with epinephrine 1:100,000 for local anesthesia, the patient developed a transient Type 1 Brugada pattern that lasted a few minutes. The whole procedure lasted 30 min. The patient's discharge to ward occurred 3 h after the end of GA. The perioperative management of ammonia, reduction of stress, and administration of drugs tolerated in Type 1 citrullinemia and Brugada pattern allowed the successful and uneventful administration of GA in the study patient.

Loading dose plus continuous/extended infusion versus intermittent bolus of ß-lactams for the treatment of Gram-negative bacteria bloodstream infections: a propensity score-adjusted retrospective cohort study.

BACKGROUND: Optimal ß-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated. METHODS: This is a retrospective observational study enrolling patients with GNB-BSIs treated with ß-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model. RESULTS: Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. ß-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, ß-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011). CONCLUSIONS: The use of LD + EI/CI of ß-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.

Heart transplant in a Sars-CoV-2 positive recipient: Management protocol of the world's first case.

The advent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in China at the end of 2019 has developed into a global outbreak, and COVID- 19 is an ongoing major public health issue. During the pandemic, transplant programs had to devise strategies to deal with the possibility of COVID-19-positive donors and recipients. We describe the case of a heart transplant recipient who tested positive with the SARS- CoV2 swab upon admission to our Unit of Cardiac Surgery when a suitable donor became available. Given his clinical status of end-stage heart failure and the absence of imaging and clinical signs suggestive of COVID-19, and his having been vaccinated with three doses, we decided to proceed with the transplant.

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study.

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64-78) vs. 62 (IQR 52-69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6-8) vs. 4 (IQR 2-6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9-11) vs. 9 (IQR 7-11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04-1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19-0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17-0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option.

Lung Ultrasound to Determine the Effect of Lower vs. Higher PEEP on Lung Aeration in Patients without ARDS-A Substudy of a Randomized Clinical Trial.

BACKGROUND: Ventilation with lower positive end-expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). METHODS: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty-seven patients underwent a systematic 12-region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. RESULTS: Thirty-three and twenty-four patients received ventilation with lower PEEP (median PEEP 1 (0-5) cm H2O) or higher PEEP (median PEEP 8 (8-8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (-2 to 3)) in the lower PEEP group, and 7 (2-11) and 6 (1-12) (difference 0 (-2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. CONCLUSIONS: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration.

Impact of a Pro-Active Infectious Disease Consultation on the Management of a Multidrug-Resistant Organisms Outbreak in a COVID-19 Hospital: A Three-Months Quasi-Experimental Study.

BACKGROUND: Antimicrobial and diagnostic stewardship (AS/DS) principles are crucial for the management of multidrug-resistant organisms (MDROs) infections. We evaluated the impact of a pro-active Infectious Disease (ID) consultation on the mortality risk of patients during an MDROs outbreak in a COVID-19 hospital. METHODS: A quasi-experimental study was performed in a dedicated COVID-19 hospital, including patients with suspected/confirmed infection and/or colonization by MDROs, which were managed as follows: (i) according to the standard of care during the pre-phase and (ii) in collaboration with a dedicated ID team performing a pro-active bedside evaluation every 48-72 h in the post-phase. RESULTS: Overall, 112 patients were included (pre-phase = 89 and post-phase = 45). The AS interventions included the following: therapy optimization (33%), de-escalation to narrow the spectrum (24%) or to lessen toxic drugs (20%), and discontinuation of antimicrobials (64%). DS included the request of additional microbiologic tests (82%) and instrumental exams (16%). With the Cox model, after adjusting for age, sex, COVID-19 severity, infection source, etiological agents, and post-phase attendance, only age predicted an increased risk of mortality, while attendance in the post-phase resulted in a decreased risk of mortality. CONCLUSIONS: Implementation of AS and DS intervention through a pro-active ID consultation may reduce the risk of 28-day mortality of COVID-19 patients with MDROs infections.

Low Back Pain and Radiofrequency Denervation of Facet Joint: Beyond Pain Control-A Video Recording.

Chronic low back pain is often due to L5S1 instability resulting in facet joint syndrome. Patients suffering from low back pain may also have a gait pattern characterized by a reduced speed and a shorter, asymmetrical step in order to reduce pain. This case is of a patient with L5S1 instability that occurred after L1 to L5 lumbar stabilization who was treated with radiofrequency (RF) denervation of the medial branch of L5S1 bilaterally. RF ablation outcome was tested by comparing its impact on pain, function, quality of life, and on gait pattern, before and 1 month after the procedure. To objectify the impact of a good pain control on gait, a video recording was performed (see Video 1).