Francesco Alessandri

Characterization of trabecular bone by dipolar demagnetizing field MRI

A multiple spin‐echo (MSE) sequence has been applied for the first time to study trabecular bone ex vivo. The second echo generated by the demagnetizing field presents discrete drops in signal intensity for certain values of the pitch of the magnetization helix created by the correlation gradient. These dips may reflect characteristic pore sizes in the trabecular bone specimens. This hypothesis is supported by similar experiments performed on a phantom with uniform pore size distribution. Trabecular bone images weighted in the MSE contrast mechanism are reported. Magn Reson Med 46:683–689, 2001.

Characterization of porous media structure by non linear NMR methods.

In this paper we discuss the possibility of modifying the multiple spin echoes existing theory, developed for a homogeneous system, to describe also an inhomogeneous system such as a porous medium. We report here the first experimental application of MSE methods to materials like travertine. The ratio A(2)/A(1) from water in travertine presents minima for characteristic values of the delay time tau, like what was previously observed in the trabecular bone. By a judicious choice of the delay time tau and of the G gradient strength, the MSE sequence can be made sensitive to a specific length-scale of the sample heterogeneity. Furthermore the MSE image shows a particular new contrast that makes the non linear NMR method very attractive for the assessment of variations of the porous structure in porous systems.

Multiple spin echoes for the evaluation of trabecular bone quality

We report a simple and efficient MR method for the evaluation of trabecular bone quality. This technique is based on detection and imaging of Multiple Spin-Echoes (MSE), a manifestation of the dipolar field generated by residual intermolecular dipolar couplings in liquids. In the particular implementation we have used, originally proposed by Bowtell [J. Magn. Reson. 100 (1992) 1; J. Magn. Reson. 88 (1990) 643; Phys. Rev. Lett. 76 (1996) 4971]. multiple spin echoes (MSE) are refocused in a two-pulse experiment in the presence of a correlation linear magnetic field gradient Gc. This gradient generates a magnetisation helix and results in the spatial modulation of the sample magnetisation. In heterogeneous systems, the amplitude of the MSE signal depends on sample heterogeneity over a distanced= π.(γ/Gcτ) which is half a cycle of the magnetisation helix, thus providing a novel contrast mechanism that can be tuned to a specific length scale. We have exploited this mechanism to study young bovine trabecular bone samples ex-vivo. We show that MSE images present a different contrast from conventional MR images, and that, by varying the experimental parameters, the image contrast can be related to specific trabecular pore sizes. The potential of this technique for the early diagnosis of osteoporotic diseases is discussed.

The Role of Rescue Therapies in the Treatment of Severe ARDS

ARDS is characterized by a non-cardiogenic pulmonary edema with bilateral chest radiograph opacities and hypoxemia refractory to oxygen therapy. It is a common cause of admission to the ICU due to hypoxemic respiratory failure requiring mechanical ventilation. Corticosteroids are not recommended in ARDS patients. Rescue therapies alleviate hypoxemia in patients unable to maintain reasonable oxygenation: recruitment maneuvers, prone positioning, inhaled nitric oxide, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation improve oxygenation, but their impact on mortality remains unproven. Restrictive fluid management seems to be a favorable strategy with no significant reduction in 60-d mortality. Future studies are needed to clarify the efficacy of these therapies on outcomes in patients with severe ARDS, and institution of these therapies may be considered on a case-by-case basis.

Specific dynamic of serum procalcitonin in critically ill patients affected by Gram-negative bacilli septic thrombophlebitis

We read with interest the study by Thomas-Rüddel et al. [1] evaluating the influence of specific pathogens and different foci of infections on serum procalcitonin (PCT) concentrations. The authors concluded that PCT levels were higher in patients with Gram-negative bacteremia compared with patients with Gram-positive or fungal diseases, whereas urogenital and abdominal foci of infection were associated with twofold increased PCT values, independent of causative pathogen. Unfortunately, this study did not provide data on PCT trends in patients affected by endovascular infections. We recently collected a small series of 13 cases of endovascular infections caused by thrombophlebitis due to Gram-negative bacilli (GNB) in the intensive care unit (ICU) of a large University Hospital in Italy. The mean age of patients enrolled was 59.2 ± 13.6 years with a predominance of male sex (61.5%); the mean SAPS II at the admission was 39.7 ± 8.1 points and the most frequent cause of ICU admission was a recent polytrauma (84.6%). All patients had persistent bacteremia despite administration of in vitro active antibiotics and removal of intravascular devices. The diagnosis of septic thrombophlebitis was corroborated by CT scan (53.8%) or echodoppler (46.2%), and thrombus appositions mainly involved aortic trunks (61.5%). The blood isolates were four Klebsiella pneumoniae, four Acinetobacter baumannii, one Enterobacter spp., one Pseudomonas aeruginosa, one Morganella morganii, one Providencia rettgeri, and one Klebsiella oxytoca. Despite the prolonged duration of bacteremia and the appropriate antibiotic therapy, all patients showed an indolent clinical course, with no multi-organ failure, prompt clinical improvement, and rapid decrease of plasma PCT concentrations within normal ranges after the onset of septic episodes (Fig. 1). As previously reported, PCT is produced in response to inflammatory cytokines and bacterial endotoxins [2]. In our cases the rapid decrease of PCT, followed by a stable normalization of serum concentration despite persistence of bacteremia, could be explained with the well-known mechanism of immune tolerance: in fact the selective blocks of some pro-inflammatory pathways, activated by bacterial endotoxins or cytokines, could impact on the production of PCT and favor a long indolent clinical course, even in the face of microbial eradication failure [3]. In conclusion, we think that our data could contribute to complete the results of Thomas-Rüddel et al. and are worthy of being further investigated in a

Extracorporeal CO2 Removal May Improve Renal Function of Patients with ARDS and Acute Kidney Injury

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Prone Positioning for ARDS: still misunderstood and misused

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by a non-cardiogenic pulmonary edema with bilateral chest X-ray opacities and hypoxemia refractory to oxygen therapy and low level of positive end-expiratory pressure (1).

Comparison of septic shock due to MDR Acinetobacter baumannii or Klebsiella pneumoniae carbapenemase—producing K. pneumoniae in ICU patients

ABSTRACT A significant cause of mortality in the intensive care unit (ICU) is multidrug-resistant (MDR) Gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp). The aim of the present study was to compare the clinical features, therapy, and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. We retrospectively analyzed patients admitted to the ICU of a teaching hospital from November 2010 to December 2015 who developed septic shock due to MDR-AB or KPC-Kp infection. Data from 220 patients were analyzed: 128 patients (58.2%) were diagnosed with septic shock due to KPC-Kp, and 92 patients (41.8%) were diagnosed with septic shock due to MDR-AB. The 30-day mortality rate was significantly higher for the MDR-AB group than the KPC-Kp group (84.8% versus 44.5%, respectively; P < 0.001). Steroid exposure and pneumonia were associated with MDR-AB infection, whereas hospitalization in the previous 90 days, primary bacteremia, and KPC-Kp colonization were associated with KPC-Kp infection. For patients with KPC-Kp infections, the use of ≥2 in vitro-active antibiotics as empirical or definitive therapy was associated with higher 30-day survival, while isolation of colistin-resistant strains was linked to mortality. Patients with MDR-AB infections, age >60 years, and a simplified acute physiology score II (SAPS II) of >45 points were associated with increased mortality rates. We concluded that septic shock due to MDR-AB infection is associated with very high mortality rates compared to those with septic shock due to KPC-Kp. Analysis of the clinical features of these critically ill patients might help physicians in choosing appropriate empirical antimicrobial therapy.

Mechanical ventilation: we have come a long way but still have a long road ahead

www.thelancet.com/respiratory Published online November 8, 2017 http://dx.doi.org/10.1016/S2213-2600(17)30431-9 1 Published Online November 8, 2017 http://dx.doi.org/10.1016/ S2213-2600(17)30431-9 Mechanical ventilation is used to sustain life in patients with acute respiratory failure and its growing use has outpaced the need for studies investigating the efficacy of the technique. Nevertheless, increasing knowledge about the physiology of mechanical ventilation led to many clinical trials assessing different ventilator settings and interventions, resulting in an increasingly complex procedure. These clinical trials found that although mechanical ventilation restores respiratory function, the settings used in mechanical ventilation are vital for patient survival. For example, in patients who have abnormal gas-exchange, mechanical ventilation normalises arterial gases, but mortality rates remain high due to multiple organ failure. Non-invasive ventilation, assisted modes of ventilator support, and protective ventilation strategies to decrease the risk of ventilator-induced lung injury, have changed the practice of mechanical ventilation considerably. Broad implementation of these interventions would be expected in clinical practice for the provision of high quality health care. However, the adoption of these interventions has been delayed. Several reasons could explain this delay. First, evidence supporting the use of non-invasive ventilation in patients with hypoxaemic respiratory failure is contradictory. A small randomised clinical trial showed that non-invasive ventilation in these patients prevented intubation and had clinical benefit. Subsequent studies have shown that non-invasive ventilation in patients with acute respiratory distress syndrome is associated with an increased risk of death (hazard ratio 1·45 [95% CI 1·16–1·80]) and treatment with high-flow oxygen results in a significantly better survival than with non-invasive ventilation. Moreover, patients with acute respiratory failure on non-invasive ventilation might have a high respiratory drive that generates large tidal volumes and considerable fluctuations in transpulmonary pressure, which might cause lung damage similar to ventilator-induced lung injury. Second, a clinical trial done in 128 patients with acute respiratory failure showed that compared with conventional pressure support ventilation, neurally adjusted ventilatory assist—a mode of mechanical ventilation that provides pressure that is proportional to inspiratory effort—is safe and feasible, but does not decrease the need for transition from assisted to controlled mechanical ventilation. Third, Weiss and coworkers showed that the protective ventilator strategy is administered to less than 20% of patients with acute respiratory distress syndrome. For patients who were ventilated using protective ventilation, the technique was used for less than 60% of the recommended time and was often started after a considerable delay. A prospective study done in 459 intensive care units across 50 countries showed that a third of patients received a tidal volume that was higher than the volume recommended to minimise ventilator-induced lung injury. These observations might be explained by the difficulties of implementing low ventilator volumes and pressures in patients who are hypoxaemic with hypercapnia and might explain the increased interest in partial or total extracorporeal support. The heterogeneity of patients with acute respiratory failure, and the variability in the risk and response profiles of mechanical ventilation make the design of the future trials particularly challenging. Adaptive study designs (ie, the adjustment of the target sample size in response to accumulating data) and enrichment designs (ie, inclusion of patients in whom physiological measurements suggest greatest benefit) should be implemented in future trials. An example of this innovative design is the Strategy of UltraProtective lung ventilation with Extracorporeal CO2 Removal for New Onset moderate to seVere ARDS (SUPERNOVA) trial (ClinicalTrials.gov identifier, NCT02282657). Extracorporeal CO2 removal (ECCO2R) is a promising approach designed to integrate the use of protective ventilation strategies in patients with acute respiratory distress syndrome, to minimise ventilator-induced lung injury, whilst enabling the management of CO2 retention and respiratory acidosis. Since baseline alterations in lung mechanics and gas-exchange considerably affect the physiological response to ECCO2R, its efficacy is likely to vary widely among patients. On the basis of the model developed by Mechanical ventilation: we have come a long way but still have a long road ahead