Infectious diseases are caused by pathogenic microorganisms and are often severe. Time to fully characterize an infectious agent after sampling and to find the right antibiotic and dose are important factors in the overall success of a patient's treatment. Previous results suggest that a nanomotion detection method could be a convenient tool for reducing antibiotic sensitivity characterization time to several hours. Here, the application of the method for slow-growing bacteria is demonstrated, taking Bordetella pertussis strains as a model. A low-cost nanomotion device is able to characterize B. pertussis sensitivity against specific antibiotics within several hours, instead of days, as it is still the case with conventional growth-based techniques. It can discriminate between resistant and susceptible B. pertussis strains, based on the changes of the sensor's signal before and after the antibiotic addition. Furthermore, minimum inhibitory and bactericidal concentrations of clinically applied antibiotics are compared using both techniques and the suggested similarity is discussed.
The insurgence of newly arising, rapidly developing health threats, such as drug‐resistant bacteria and cancers, is one of the most urgent public‐health issues of modern times. This menace calls for the development of sensitive and reliable diagnostic tools to monitor the response of single cells to chemical or pharmaceutical stimuli. Recently, it has been demonstrated that all living organisms oscillate at a nanometric scale and that these oscillations stop as soon as the organisms die. These nanometric scale oscillations can be detected by depositing living cells onto a micro‐fabricated cantilever and by monitoring its displacements with an atomic force microscope‐based electronics. Such devices, named nanomotion sensors, have been employed to determine the resistance profiles of life‐threatening bacteria within minutes, to evaluate, among others, the effect of chemicals on yeast, neurons, and cancer cells. The data obtained so far demonstrate the advantages of nanomotion sensing devices in rapidly characterizing microorganism susceptibility to pharmaceutical agents. Here, we review the key aspects of this technique, presenting its major applications. and detailing its working protocols.
Antibody-mediated rejection (AMR) remains one of the most critical problems in renal transplantation, with a significant impact on patient and graft survival. In the United States, no treatment has received FDA approval jet. Studies about treatments of AMR remain controversial, limited by the absence of a gold standard and the difficulty in creating large, multi-center studies. These limitations emerge even more in pediatric transplantation because of the limited number of pediatric studies and the occasional use of some therapies with unknown and poorly documented side effects. The lack of recommendations and the unsharp definition of different forms of AMR contribute to the challenging management of the therapy by pediatric nephrologists. In an attempt to help clinicians involved in the care of renal transplanted children affected by an AMR, we rely on the latest recommendations of the Transplantation Society (TTS) for the classification and treatment of AMR to describe treatments available today and potential new treatments with a particular focus on the pediatric population.
Background Circulatory shock and multi-organ failure remain major contributors to mortality in critically ill patients, resulting in decoupling of macro- and microcirculatory function. Recent studies have identified the recruitment of microcirculatory diffusion capacity as reflected by an increase in functional capillary density (FCD) in response to a topical nitroglycerin (NG) administration as a mechanism to increase oxygen delivery to the tissue. However, the effect of circulatory shock on microcirculatory recruitability remains unclear. We hypothesized that circulatory shock leads to microcirculatory de-recruitment reflected by a lower FCD and lower RBCv, similar maximum recruitable FCD (FCDNG) and RBCV (RBCvNG), and increased microcirculatory recruitability (ΔFCDNG and ΔFCDNG). Methods Sublingual handheld vital microscopy measurements and assessment of microcirculatory recruitability were performed after initial fluid resuscitation in mechanically ventilated patients consecutively admitted to the tertiary medical ICU of the university hospital of Zurich. The presence of circulatory shock was defined as > 3 of the following: cardiac index (CI) < 2.2 l/min/m2, lactate > 2 mmol/l, vasopressor dependent index (VDI) > 3, Mottling score ≥ 2, capillary refill time (CRT) > 3s, mean arterial pressure (MAP) < 65 mmHg or the use of ECLC. FCD, FCDNG, and ΔFCDNG were assessed using the MicroTools advanced computer vision algorithm. Results 54 patients (57 ± 14y, BMI 26.3 ± 4.9kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of which with circulatory shock (6 cardiogenic, 4 septic, 3 other). As compared to the controls, patients with circulatory shock presented with similar CI and MAP, but higher heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), CRT (p < 0.01), and Mottling score (p < 0.001). FCD and FCDNG were 15% and 10% lower in patients with circulatory shock (18.9 ± 3.2 to 16.9 ± 4.2, p < 0.01; 21.3 ± 2.9 to 19.3 ± 3.1; p = 0.03), while ΔFCDNG and ΔRBCvNG remained similar. Conclusion In patients presenting with comparable macrocirculatory status but clinical signs of impaired microcirculation and tissue hypoxia, monitoring of the sublingual microcirculation revealed signs of capillary de-recruitment and loss of recruitability potential suggesting microcirculatory tamponade associated with fluid resuscitation. These results indicate a potential benefit of monitoring microcirculation in critically ill patients in shock.
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