The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003−2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36−23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28−52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011−1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091−4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001−1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/µL on POD 7 (OR 16.1 (95% CI: 1.31−195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97−63.18), p = 0.048), NK cells < 125 cells/µL on POD 3 (OR 6.97 (95% CI: 3.81−12.7), p < 0.01), basophils < 18.1 cells/µL on POD 10 (OR 3.45 (95% CI: 1.37−12.3), p = 0.02) and mDC < 4.7 cells/µL on POD 7 (OR 11.68 (95% CI: 1.85−73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and­by diligent clinical management­even prevent deteriorated outcome due to IRI and eRGI after KT.

Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective.

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.

Neutrophil-to-lymphocyte ratio is associated with increased cerebral blood flow velocity in acute bacterial meningitis.

In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients' demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients', radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9-14] vs. 14 [11-15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4-30.2] vs. normal CBFv:13.5 [8.4-19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003-1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients' prognosis.

Brainhack: Developing a culture of open, inclusive, community-driven neuroscience.

Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.

Increased Neutrophil-to-Lymphocyte Ratio is Associated with Unfavorable Functional Outcome in Acute Ischemic Stroke.

BACKGROUND: Inflammatory response is the hallmark of secondary brain injury in stroke patients. Neutrophil-to-lymphocyte ratio (NLR) emerged as a marker for functional outcome in several diseases. OBJECTIVES: To investigate the association between NLR on admission and during hospital stay and functional outcome in acute ischemic stroke (AIS). METHODS: This observational study included all consecutive AIS patients admitted at a German stroke center covering 2011-2013. Patient characteristics and clinical data were retrieved from institutional databases. Multivariate analysis was conducted to investigate parameters associated with functional outcome. Receiver operating characteristic (ROC) analysis was performed to identify the best cutoff for NLR to discriminate between favorable and unfavorable functional outcome. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on functional outcome. RESULTS: A total of 807 patients with AIS were included for analysis. Patients with worse functional outcome at 3 months were older and had worse clinical status on admission, higher rates of infectious complications, and an increased NLR. ROC analysis identified a NLR of 3.3 as best cutoff value to discriminate between favorable and unfavorable functional outcomes (area under the curve 0.693, p < 0.001, Youden's index = 0.318; p < 0.001; sensitivity 68.5%, specificity 63.9%). Propensity-matched analysis still demonstrated a higher rate of unfavorable functional outcome at 3 months in patients with NLR ≥ 3.3 [modified Rankin scale 3-6 at 3 months: NLR ≥ 3.3 51.5% vs. NLR < 3.3 36.4%; p = 0.002]. CONCLUSIONS: In AIS patients we identified NLR as an important predictor for unfavorable functional outcome.