Microbiological diagnostics of bloodstream infections in Europe—an ESGBIES survey

ObjectivesHigh-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories.MethodsWe performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries.ResultsResponses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC.ConclusionsLaboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.     

Prognostic Performance of the Augmented Hematopoietic Cell Transplantation-Specific Comorbidity/Age Index in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation from Alternative Graft Sources

The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was developed and validated to weigh the burden of pretransplantation comorbidities and estimate their impact on post-transplantation risks of nonrelapse mortality (NRM). Recently, the HCT-CI was augmented by the addition of both age and the values of 3 markers: ferritin, albumin, and platelet count. So far, research involving The HCT-CI has been limited almost exclusively to recipients of allogeneic hematopoietic cell transplantation (HCT) from HLA-matched grafts. To this end, we sought to investigate the discriminative capacity of an augmented comorbidity/age index among 724 recipients of allogeneic HCT from HLA-mismatched (n = 345), haploidentical (n = 117), and umbilical cord blood (UCB; n = 262) grafts between 2000 and 2013. In the overall cohort, the augmented comorbidity/age index had a higher c-statistic estimate for prediction of NRM compared with the original HCT-CI (.63 versus .59). Findings were similar for recipients of HLA-mismatched (.62 versus .59), haploidentical (.60 versus .54), or UCB grafts (.65 versus .61). Compared with patients with an HCT-CI score ≥4, those with a score <4 had a higher survival rate among recipients of HLA-mismatched (55% versus 39%; P < .0008), HLA-haploidentical (58% versus 38%; P = .01), or UCB (67% versus 48%; P = .004) grafts. Our results demonstrate the utility of the augmented comorbidity/age index as a valid prognostic tool among recipients of allogeneic HCT from alternative graft sources.     

Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients

Purpose

Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level.

Methods

Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O₂ and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed.

Results

At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT.

Conclusion

IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.

     

Examining the service‐related experiences and outcomes of caregivers involved in a system of care who experienced everyday discrimination

Individuals who report everyday experiences of discrimination are at heightened risk for adverse health outcomes and tend to report underutilization of health services. Systems of care (SOCs) have the potential to engage members of minority groups and to reduce health disparities. We examined the service‐related experiences of predominantly Latinx caregivers enrolled in a SOC for their children with severe psychological health needs. We used independent samples t‐tests and regression analyses to compare relations among service access, perceived service characteristics, and caregiver stress according to whether caregivers reported frequent or infrequent discrimination. The frequent discrimination group scored significantly higher on dimensions of stress and had greater dosage than the infrequent group. There were no differences in relations between service characteristics and outcomes by group. Findings indicated important differences in the service‐related experiences and outcomes of caregivers who reported frequent and infrequent discrimination. We discuss limitations and implications.     

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain‐relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.     

New insights into a spectrum of developmental malformations related to mTOR dysregulations: challenges and perspectives

In recent years the role of the mammalian target of rapamycin (mTOR) pathway has emerged as crucial for normal cortical development. Therefore, it is not surprising that aberrant activation of mTOR is associated with developmental malformations and epileptogenesis. A broad spectrum of malformations of cortical development, such as focal cortical dysplasia (FCD) and tuberous sclerosis complex (TSC), have been linked to either germline or somatic mutations in mTOR pathway‐related genes, commonly summarised under the umbrella term ‘mTORopathies’. However, there are still a number of unanswered questions regarding the involvement of mTOR in the pathophysiology of these abnormalities. Therefore, a monogenetic disease, such as TSC, can be more easily applied as a model to study the mechanisms of epileptogenesis and identify potential new targets of therapy. Developmental neuropathology and genetics demonstrate that FCD IIb and hemimegalencephaly are the same diseases. Constitutive activation of mTOR signalling represents a shared pathogenic mechanism in a group of developmental malformations that have histopathological and clinical features in common, such as epilepsy, autism and other comorbidities. We seek to understand the effect of mTOR dysregulation in a developing cortex with the propensity to generate seizures as well as the aftermath of the surrounding environment, including the white matter.