Before the availability of mRNA vaccines, many transplant centers chose to significantly reduce maintenance immunosuppression in kidney transplant recipients (KTRs) with SARS‐CoV‐2 infection. The extent to which this increases the risk of allosensitization is unclear.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tid.14052

Association between PIRCHE‐II scores and de novo allosensitization after reduction of immunosuppression during SARS‐CoV‐2 infection in kidney transplant recipients

Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR. Eculizumab (900 mg IV) led to complete inhibition of the terminal complement cascade (unremarkable AP50 and CH50 activity) and prompt stoppage of complement-dependent antibody-mediated allograft injury (clearance of intra-graft C4d and C5b-9 deposition). Despite complement inhibition, obinutuzumab (1000 mg IV) determined full and long-lasting peripheral B-cell depletion, with significant reduction in all DSA. Graft function improved, remaining stable up to three years of follow-up. No signs of active ABMR and rebound DSA were detected. Obinutuzumab B-cell depletion and inhibition of DSA production were not affected by complement blockage. Further studies are needed to confirm the potential benefit of obinutuzumab in association with complement inhibitors. 

Sequential administration of anti-complement component C5 eculizumab and type-2 anti-CD20 obinutuzumab for the treatment of early antibody-mediated rejection after kidney transplantation: A proof of concept.

Machine learning was characterized by building models and finding correlations between data features, while logistic regression, decision trees, support vector machines (SVM), random forest (RF) and neural networks were recognized as common ML approaches. Bayesian modeling model uncertainty, which can estimate the features from the dataset directly instead of from sampling distribution. Their roles were extremely useful for the detection and progression for diseases in neuroscience. This review summarize different approaches in various diseases, hoping to introduce the potential roles of biostatistics tools in neuroscience. 

pdf/a-survey-on-common-biostatistics-tools-in-neuroscience-4g72qhpfxa.pdf

A survey on common biostatistics tools in neuroscience: Machine learning and Bayesian modeling

INTRODUCTION
Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.


METHODS
Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models.


RESULTS
In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings.


DISCUSSION
Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials.


HIGHLIGHTS
SCD in amyloid-positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

Advances in hematopoietic cell transplantation have expanded the use of alternative donors such as haploidentical family donors or mismatched unrelated donors. However, donor-specific HLA antibodies (DSA) have been recognized as a significant risk factor of primary graft failure after HLA incompatible transplantation. Therefore, screening for HLA antibodies and taking DSA into consideration in the process of donor search play an increasingly important role in donor selection. If an HLA compatible donor is not available, desensitization may enable a successful transplantation. In this review, we describe the currently most widely used methods for HLA antibody detections including their pitfalls. In addition, we summarize the results of the studies on the impact of preformed DSA on transplant outcomes and their treatment options. Many more and larger studies are needed to clarify laboratory issues as well as immunological and clinical aspects in the management of DSA. 

Relevance of donor-specific HLA antibodies in hematopoietic cell transplantation

Background: Cognitive decline is a key outcome of clinical studies in Alzheimer’s disease (AD). Objective: To determine effects of global amyloid load as well as hippocampus and basal forebrain volumes on longitudinal rates and practice effects from repeated testing of domain specific cognitive change in the AD spectrum, considering non-linear effects and heterogeneity across cohorts. Methods: We included 1,514 cases from three cohorts, ADNI, AIBL, and DELCODE, spanning the range from cognitively normal people to people with subjective cognitive decline and mild cognitive impairment (MCI). We used generalized Bayesian mixed effects analysis of linear and polynomial models of amyloid and volume effects in time. Robustness of effects across cohorts was determined using Bayesian random effects meta-analysis. Results: We found a consistent effect of amyloid and hippocampus volume, but not of basal forebrain volume, on rates of memory change across the three cohorts in the meta-analysis. Effects for amyloid and volumetric markers on executive function were more heterogeneous. We found practice effects in memory and executive performance in amyloid negative cognitively normal controls and MCI cases, but only to a smaller degree in amyloid positive controls and not at all in amyloid positive MCI cases. Conclusions: We found heterogeneity between cohorts, particularly in effects on executive functions. Initial increases in cognitive performance in amyloid negative, but not in amyloid positive MCI cases and controls may reflect practice effects from repeated testing that are lost with higher levels of cerebral amyloid.

Cognitive Trajectories in Preclinical and Prodromal Alzheimer’s Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach

It is still not fully elucidated which pretransplant donor‐specific HLA antibodies (DSA) are harmful after kidney transplantation. In particular, it needs to be clarified whether cumulative mean fluorescence intensities (MFI) against multiple HLA specificities have a predictive value for allograft function. Our retrospective single centre study analyzed preformed HLA antibodies determined by Luminex™ Single Antigen Bead (SAB) assay, including C1q addition, in relation to rejection and clinical outcome in 255 cross match negative kidney allograft recipients. Only 33 recipients (13%) of the total cohort showed early AMR during the first year posttransplant, but in patients with pre‐transplant DSA the rate was increased to 15 out of 40 (38%). Three year graft survival was significantly shorter in patients with histological signs of AMR compared with patients without AMR or with no biopsy (74%, 92%, and 97%, respectively, p < 0.0001). In patients with HLA‐DSA, a cumulative MFI value of all HLA antibodies of more than 103.000 indicated the highest risk for AMR posttransplant (p = 0.01). In conclusion, in patients with HLA‐DSA, the cumulative MFI value may help to further stratify the risk of AMR after kidney transplantation.

Cumulative mean fluorescent intensities of HLA specific antibodies predict antibody mediated rejections after kidney transplantation

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Cognitive Trajectories in Preclinical and Prodromal Alzheimer’s Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach

Cumulative mean fluorescent intensities of HLA specific antibodies predict antibody mediated rejections after kidney transplantation