Relationship between Pharmacokinetic/Pharmacodynamic Target Attainment and Microbiological Outcome in Critically Ill COVID-19 Patients with Documented Gram-Negative Superinfections Treated with TDM-Guided Continuous-Infusion Meropenem

Objectives: The objective of this study was to explore the relationship between pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous-infusion (CI) meropenem and microbiological outcome in critical COVID-19 patients with documented Gram-negative superinfections. Methods: Patients receiving CI meropenem for documented Gram-negative infections at the COVID ICU of the IRCCS Azienda Ospedaliero-Universitaria di Bologna and undergoing therapeutic drug monitoring from January 2021 to February 2022 were retrospectively assessed. Average steady-state meropenem concentrations (C-ss) were calculated and the C-ss/MIC ratio was selected as a pharmacodynamic parameter of meropenem efficacy. The C-ss/MIC ratio was defined as optimal if >= 4, quasi-optimal if between 1 and 4, and suboptimal if <1. The relationship between C-ss/MIC and microbiological outcome was assessed. Results: Overall, 43 critical COVID-19 patients with documented Gram-negative infections were retrieved. Combination therapy was implemented in 26 cases. C-ss/MIC ratios were optimal in 27 (62.8%), quasi-optimal in 7 (16.3%), and suboptimal in 9 cases (20.9%). Microbiological failure occurred in 21 patients (48.8%), with no difference between monotherapy and combination therapy (43.8% vs. 53.8%; p = 0.53). The microbiological failure rate was significantly lower in patients with an optimal C-ss/MIC ratio compared to those with a quasi-optimal or suboptimal C-ss/MIC ratio (33.3% vs. 75.0%; p = 0.01). Conclusion: Suboptimal attainment of meropenem PK/PD targets may be a major determinant impacting on microbiological failure in critical COVID-19 patients with Gram-negative superinfections

A "mysterious" intrabdominal mass with infectious origin, in a patient with HIV infection under control. A "delayed diagnosis" allows to enlarge our knowledge, by assessing a rare disease

A probable case report of an abdominal botryomycosis has been hypothesized in a patient with a stable HIV infection under an effective antiretroviral therapy. Hyperpyrexia, abdominal pain and tenderness, and a thickening of small intestinal walls associated with multiple mesenteric adenopathies and a peritoneal involvement, prompted an ultrasonography-guided fine needle biopsy, and later a laparoscopy-laparotomy which excluded a neoplastic or lymphoproliferative disorders, showing only abundant fibrotic and necrotic-steatonecrotic tissue, with sparse multinuclear giant cells type Langhans. The prompt response to surgical intervention and a treatment with i.v. meropenem alone might be referred to a concurrent gram-negative infection of abdominal origin, until a late culture of an atypical Mycobacterium came to our attention over one month after the end of hospitalization. An updated literature search is presented and discussed, in relationship with the observed, extremely infrequent case reports of botryomycosis in different clinical settings

Experimental determination of viscous damper parameters in low velocity ranges

In the last decades many strategies for seismic vulnerability mitigation of structures have been developed through analytical studies and experimental tests. Among these, energy dissipation by external devices assumes a great relevance for the relative design simplicity, even if applied to complex structures, and the effectiveness in reducing seismic demand. In particular, the use of fluid viscous dampers represents a very attractive solution because of their velocity-dependent behaviour and relatively low costs. The application on structures requires specific study under seismic excitation and a particular care of structural details. In this context the use of proper constitutive models for the dampers assumes a fundamental role. Seismic codes, as well as literature models generally provide a velocity-dependent relationship with two characteristic constants defining the shape of the force-displacement curve. In this paper an experimental campaign aimed at the determination of the damper constants in the range of low velocities is presented. A fluid viscous damper is tested with different ramp velocity functions. Results show that the assumption of velocity independence of the damper constants fails for the case of low velocity, giving rise to new issues about the limit of validity of the constitutive models generally adopted for viscous dampers

FE modeling of Partially Steel-Jacketed (PSJ) RC columns using CDP model

This paper deepens the finite element modeling (FEM) method to reproduce the compressive behavior of partially steel-jacketed (PSJ) RC columns by means of the Concrete Damaged Plasticity (CDP) Model available in ABAQUS software. Although the efficiency of the CDP model is widely proven for reinforced concrete columns at low confining pressure, when the confinement level becomes high the standard plasticity parameters may not be suitable to obtain reliable results. This paper deals with these limitations and presents an analytically based strategy to fix the parameters of the Concrete Damaged Plasticity (CDP) model. Focusing on a realistic prediction of load-bearing capacity of PSJ RC columns subjected to monotonic compressive loads, a new strain hardening/softening function is developed for confined concrete coupled with the evaluation of the dilation angle including effects of confinement. Moreover, a simplified efficient modeling approach is proposed to take into account also the response of the steel angle in compression. The prediction accuracy from the current model is compared with that of existing experimental data obtained from a wide range of mechanical confinement ratio

A new hybrid procedure for the definition of seismic vulnerability in Mediterranean cross-border urban areas

Assessment of seismic vulnerability of urban areas provides fundamental information for activities of planning and management of emergencies. The main difficulty encountered when extending vulnerability evaluations to urban contexts is the definition of a framework of assessment appropriate for the specific characteristics of the site and providing reliable results with a reasonable duration of surveys and post-processing of data. The paper proposes a new procedure merging different typologies of information recognized on the territories investigated and for this reason called ‘‘hybrid.’’ Knowledge of historical events influencing urban evolution and analysis of recurrent building technologies are used to evaluate the vulnerability indexes of buildings and building stocks. On the other hand, a vulnerability model is calibrated by means of experimental and numerical investigations on prototype buildings representative of the most recurrent typologies. In the final framework, the vulnerability index, calculated through simplified assessment forms, is linked to the seismic intensity expressed by the peak ground acceleration and associated with an index of damage expressing the economical loss. The procedure has been tested on the urban center of Lampedusa island (Italy) providing as the output vulnerability index maps, vulnerability curves, critical PGA maps, and estimation of the economical damage associated with different earthquake scenarios. The application of the procedure can be suitably repeated for medium-to-small urban areas, typically recurring in the Mediterranean by carrying out each time a recalibration of the vulnerability mode

Stress-strain models for normal and high strength confined concrete: Test and comparison of literature models reliability in reproducing experimental results

The adoption of proper constitutive laws for confined concrete is basic for seismic assessment of new and existing reinforced concrete civil structures. The deformation capacity of reinforced concrete (RC) columns subjected to axially centred and eccentric loads depends on the effectiveness confinement action. A proper assignment of the stress-strain laws for concrete allows obtaining an adequate definition of the ductility of the cross-sections and correctly identifying mechanical nonlinearities in computational models. Several studies concerning the behaviour of confined concrete have been carried out, highlighting the role of different geometrical and mechanical parameters to the overall response of RC members in compression. In this frame, the primary aim of this paper is to discuss the reliability of the stress-strain concrete models for concrete subjected to confining stresses in the cases of normal strength concrete (NSC), and high strength concrete (HSC). A selected review of the most popular models for confined concrete available in the literature is presented and discussed together with the respective analytical formulations. Furthermore, a discussion on their reliability is carried out by comparing results coming from the implementation of each model and comparing analytical predictions with experimental data available in the literature

Empirical equations for the direct definition of stress-strain laws for fiber-section-based macromodeling of infilled frames

Equivalent strut macromodels are largely used to model the influence of infill walls in frame structures due to their simplicity and effectiveness from a computational point of view. Despite these advantages, which are fundamental to carrying out seismic simulation of complex structures, equivalent struts are phenomenological models and therefore have to conventionally account for the influence of really large amounts of geometrical and mechanical variables with a relatively simple inelastic response. Mechanical approaches, generally used to evaluate the force–displacement curve of a strut, are based on hypothesizing the damage mechanism that will occur for an infill–frame system subject to lateral forces. This assumption has a great impact on the response of the system and is affected by large uncertainties that also propagate in seismic assessment results. Based on the aforementioned unknowns, this paper proposes a new stress–strain relationship to be used for fiber-section modeling of equivalent struts. The definition of the stress–strain model is based on an empirical approach rather than a mechanical one. The four parameters defining the stress–strain law (peak stress, peak strain, ultimate stress, and ultimate strain) are directly linked to geometrical and mechanical features of an infilled frame through analytical correlation laws, which are determined from an experimental data set enlarged with data from refined finite-element (FE) simulations. The analytical correlations provided in the paper are proposed as a tool for direct modeling of an infilled frame. Validation tests were carried out with experimental results different from those used to build the data set. The extension of the model to the prediction of cyclic behavior is finally proposed

Out of plane fragility of infill walls with and without prior in-plane damage

The paper presents the results of a probabilistic assessment framework aimed at evaluating out-of-plane fragility curves of infill walls which have suffered (or not) prior in-plane damage. Out-of-plane incremental dynamic analyses are performed based on a suite of 22 ground motion records. A recently developed in-plane / out-of-plane macroelement model is used to model masonry infills within frames. The outcomes show fragility curves representing the probability of exceeding out-of-plane collapse at a given earthquake intensity as a function of a different combination of geometrical and mechanical parameters, in-plane damage level and supporting conditions

Out-of-Plane fragility of infilled frames with and without prior damage

The paper presents the results of a probabilistic assessment framework aimed at evaluating out-of-plane fragility curves of infill walls which have suffered (or not) prior in-plane damage. Out-of-plane incremental dynamic analyses are performed based on a suite of 22 ground motion records. A recently developed in-plane / out-of-plane macroelement model is used to model masonry infills within frames. The outcomes show fragility curves representing the probability of exceeding out-of-plane collapse at a given earthquake intensity as a function of a different combination of geometrical and mechanical parameters, in-plane damage level and supporting conditions