Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis

Importance: Meropenem is a widely prescribed β-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, setting, and participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main outcomes and measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial registration: ClinicalTrials.gov Identifier: NCT03452839

Age of submarine debris avalanches and tephrostratigraphy offshore Ischia Island, Tyrrhenian Sea, Italy

We present an "event stratigraphy" framework built for the last 23 cal ka marine record in the southern offshore of Ischia Island based on AMS (14)C dating and tephrostratigraphic analysis of 11 gravity cores. Two collapse events have been recovered in the record: a) the Ischia submarine debris avalanche/debris flow (DA/DF), dated between similar to 3 ka B.P. and 2.4 ka B.P. and possibly between 2.7 ka B.P. and 2.4 ka B.P. (event DF1); b) a former, pre-Holocene, DA/DF older than 23 cal ka B.P. (event DF2). The Ischia DA, with an estimated volume of 1.5 km(3), incorporates thousands of blocks that are still detectable on the sea-floor until 45-50 km far from the island. Our results indicate an age of emplacement younger than previously thought and support the hypothesis that a major catastrophic event occurred when the island was already inhabited by Greek settlers (i.e. after the 7th century BC). Three ash layers have been recognised in the post-DF1 avalanche sequence and correlated with Ischian eruptions occurred between Middle Ages and Roman times. Two tephras recovered in the pre-DF1 succession have been correlated with explosive activity occurred on Ischia and Procida islands from similar to 23 ka to similar to 17.5 ka B.P. The results presented here improve the chronostratigraphic reconstruction of the main eruptive and collapse events that affected Ischia volcano during Late Pleistocene-Holocene and their dispersal at sea The occurrence of at least two major collapsing events in the past 23 kyr confirms the close genetic relationship between gravity failures and Mt. Epomeo uplift. (C) 2010 Elsevier B.V. All rights reserved

Age of submarine debris avalanches offshore Ischia island, Tyrrhenian Sea, Italy

Further 14C age constraints for the emplacement of historical and pre historical submarine debris avalanche and related to major collapses that affected the southern flank of Ischia island volcano are presented. Results are based on the stratigraphy of 11 gravity cores located in the southern offshore of the island and on new AMS analyses. The two collapsing events are: a) the Ischia submarine debris avalanche/debris flow, dated between ∼2.3 cal ka B.P. and ∼3 cal ka B.P.; b) a debris flow older than 23 cal ka B.P.. The Ischia debris avalanche, previously recognised mostly through marine geophysics, has an estimated volume of 1.5 km 3 and incorporates thousands of blocks that are still detectable over the sea-floor until 45-50 km from the island. Our results indicate an age of emplacement younger than previously held and support the still tentative hypothesis that a major catastrophic event occurred when the island was already inhabited by Greek settlers i.e. after the 7 th century b.C. The occurrence of at least two major collapsing events in the past 23 ka confirms the close genetic relationship between gravity failures and Mt. Epomeo uplift

P5225Biventricular morphological and functional remodeling after percutaneous aortic valve implantation: 2d strain analysis

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Asian Australasian Journal of Animal Sciences

p. 1399-1406This study aimed to establish the optimum level of palm kernel meal in the diet of Santa Ines lambs based on the sensorial characteristics and fatty acid profile of the meat. We used 32 lambs with a starting age of 4 to 6 months and mean weight of , kept in individual stalls. The animals were fed with Tifton-85 hay and a concentrate mixed with 0.0, 6.5, 13.0 or 19.5% of palm kernel meal based on the dry mass of the complete diet. These levels formed the treatments. Confinement lasted 80 days and on the last day the animals were fasted and slaughtered. After slaughter, carcasses were weighed and sectioned longitudinally, along the median line, into two antimeres. Half-carcasses were then sliced between the 12th and 13th ribs to collect the loin (longissimus dorsi), which was used to determine the sensorial characteristics and fatty acid profile of the meat. For sensorial evaluation, samples of meat were given to 54 judges who evaluated the tenderness, juiciness, appearance, aroma and flavor of the meat using a hedonic scale. Fatty acids were determined by gas chromatography. The addition of palm kernel meal to the diet had no effect on the sensorial characteristics of meat juiciness, appearance, aroma or flavor. However, tenderness showed a quadratic relationship with the addition of the meal to the diet. The concentration of fatty acids C12:0, C14:0 and C16:0 increased with the addition of palm kernel meal, as did the sum of medium-chain fatty acids and the atherogenicity index. Up to of 19.5% of the diet of Santa Ines lambs can be made up of palm kernel meal without causing significant changes in sensorial characteristics. However, the fatty acid profile of the meat was altered

Observational multicentre registry of patients treated with IMPella mechanical circulatory support device in Italy: The IMP-IT registry

Aims: The aim of this study was to investigate nationwide trends and clinical outcomes of the Impella device for cardiogenic shock (CS) and high-risk percutaneous coronary intervention (HR-PCI). Methods and results: The IMP-IT study was a multicentre observational national registry which enrolled all patients treated with Impella 2.5, Impella CP, Impella 5.0 and Impella RP, both for CS and HR-PCI indications, across 17 Italian centres from 2004 to June 2018. A total of 406 patients were included: 229 had CS (56.4%) and 177 underwent HR-PCI (43.6%). The use of Impella increased significantly during the study period (average annual percent change 39.8%, 95% confidence interval: 30.4 to 49.9; p<0.0001) for both indications. The Impella 2.5 was the most commonly used device (N=242; 59.6%). Rates of in-hospital and one-year all-cause death in patients with CS were 46.9% and 57.0%, respectively; 18.5% underwent left ventricular assist device implantation or heart transplant at one year. Rates of in-hospital and one-year allcause death in patients who underwent HR-PCI were 5.7% and 15.6%, respectively. Rates of device-related complications were 37.1% and 10.7% in the setting of CS and HR-PCI, respectively. Conclusions: Use of the Impella for CS and HR-PCI is increasing substantially in Italy, despite relatively high rates of device-related complications

Timing of Impella implantation and outcomes in cardiogenic shock or high-risk percutaneous coronary revascularization

Objective: To evaluate the role of the microaxial percutaneous mechanical circulatory support device (Impella\uae pump) implantation pre-percutaneous coronary intervention (PCI) versus during/after PCI in cardiogenic shock (CS) and high-risk PCI populations. Background: A better understanding of the safety and effectiveness of the Impella and the role of timing of this support initiation in specific clinical settings is of utmost clinical relevance. Methods: A total of 365 patients treated with Impella 2.5/CP in the 17 centers of the IMP-IT Registry were included. Through propensity-score weighting (PSW) analysis, 1-year clinical outcomes were assessed separately in CS and HR-PCI patients, stratified by timing of Impella support. Results: Pre-procedural insertion was associated with an improvement in 1-year survival in patients with CS due to acute myocardial infarction (AMI) treated with PCI (p =.04 before PSW, p =.009 after PSW) and HR-PCI (p <.01 both before and after PSW). Among patients undergoing HR-PCI, early Impella support was also associated with a lower rate of the composite of mortality, re-hospitalization for heart failure, and need for left-ventricular assist device/heart transplantation at 1-year (p =.04 before PSW, p =.01 after PSW). Furthermore, Impella use during/after PCI was associated with an increased in-hospital life-threatening and severe bleeding among patients with AMI-CS receiving PCI (7 vs. 16%, p =.1) and HR-PCI (1 vs. 9%, p =.02). Conclusions: Our findings suggested a survival benefit and reduced rates of major bleeding when a pre-PCI Impella implantation instead of during-after procedure was used in the setting of HR-PCI and AMI-CS

Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non-familial (sporadic) DCM (SDCM) across Europe. Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P\ua0<\ua00.01), had less severe disease phenotype at presentation (P\ua0<\ua00.02), more favourable baseline cardiovascular risk profiles (P\ua0 64\ua00.007), and less medication use (P\ua0 64\ua00.042). Outcome at 1\ua0year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25\u20130.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02\u20131.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P\ua0<\ua00.01) and had higher genetic yield (55% vs. 22%, P\ua0<\ua00.01). Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short-term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non-marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence