Changes in bone microarchitecture following kidney transplantation—Beyond bone mineral density

Bone disease in kidney transplant recipients (KTRs) is characterized by bone mineral density (BMD) loss but bone microarchitecture changes are poorly defined. In this prospective cohort study, we evaluated bone microarchitecture using non‐invasive imaging modalities; high‐resolution magnetic resonance imaging (MRI), peripheral quantitative computed tomography (pQCT), dual energy X‐ray absorptiometry (DXA), and the trabecular bone score (TBS) following kidney transplantation. Eleven KTRs (48.3 ± 11.2 years) underwent MRI (tibia), pQCT (radius) and DXA at baseline and 12 months post–transplantation. Transiliac bone biopsies, performed at transplantation, showed 70% of patients with high/normal bone turnover. Compared with baseline, 12‐month MRI showed deterioration in indices of trabecular network integrity—surface to curve ratio (S/C; ?15%, P = 0.03) and erosion index (EI; +19%, P = 0.01). However, cortical area increased (+10.3%, P = 0.04), with a non‐significant increase in cortical thickness (CtTh; +7.8%, P = 0.06). At 12 months, parathyroid hormone values (median 10.7 pmol/L) correlated with improved S/C (r = 0.75, P = 0.009) and EI (r = ?0.71, P = 0.01) while osteocalcin correlated with CtTh (r = 0.72, P = 0.02) and area (r = 0.70, P = 0.02). TBS decreased from baseline (?5.1%, P = 0.01) with no significant changes in BMD or pQCT. These findings highlight a post–transplant deterioration in trabecular bone quality detected by MRI and TBS, independent of changes in BMD, underlining the potential utility of these modalities in evaluating bone microarchitecture in KTRs.     

Induction of tolerance in a rat model of laryngeal transplantation

BACKGROUND: The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression. MATERIALS AND METHODS: Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism. RESULTS: All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise. CONCLUSIONS: In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.     

Perceptual rivalry across animal species

This review in memoriam of Jack Pettigrew provides an overview of past and current research into the phenomenon of multistable perception across multiple animal species. Multistable perception is characterized by two or more perceptual interpretations spontaneously alternating, or rivaling, when animals are exposed to stimuli with inherent sensory ambiguity. There is a wide array of ambiguous stimuli across sensory modalities, ranging from the configural changes observed in simple line drawings, such as the famous Necker cube, to the alternating perception of entire visual scenes that can be instigated by interocular conflict. The latter phenomenon, called binocular rivalry, in particular caught the attention of the late Jack Pettigrew, who combined his interest in the neuronal basis of perception with a unique comparative biological approach that considered ambiguous sensation as a fundamental problem of sensory systems that has shaped the brain throughout evolution. Here, we examine the research findings on visual perceptual alternation and suppression in a wide variety of species including insects, fish, reptiles, and primates. We highlight several interesting commonalities across species and behavioral indicators of perceptual alternation. In addition, we show how the comparative approach provides new avenues for understanding how the brain suppresses opposing sensory signals and generates alternations in perceptual dominance.     

Use of SARS‐CoV‐2‐infected deceased organ donors: Should we always “just say no?”

In the context of a rapidly evolving pandemic, multiple organizations have released guidelines stating that all organs from potential deceased donors with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection should be deferred, including from otherwise medically eligible donors found to have mild or asymptomatic SARS‐CoV‐2 discovered on routine donor screening. In this article, we critically examine the available data on the risk of transmission of SARS‐CoV‐2 through organ transplantation. The isolation of SARS‐CoV‐2 from nonlung clinical specimens, the detection of SARS‐CoV‐2 in autopsy specimens, previous experience with the related coronaviruses SARS‐CoV and MERS‐CoV, and the vast experience with other common RNA respiratory viruses are all addressed. Taken together, these data provide little evidence to suggest the presence of intact transmissible SARS‐CoV in organs that can potentially be transplanted, specifically liver and heart. Other considerations including ethical, financial, societal, and logistical concerns are also addressed. We conclude that, for selected patients with high waitlist mortality, transplant programs should consider accepting heart or liver transplants from deceased donors with SARS‐CoV‐2 infection.     

Differential Effect of Long-Term Systemic Exposure of TNFα on Health of the Annulus Fibrosus and Nucleus Pulposus of the Intervertebral Disc

The inflammatory cytokine tumor necrosis factor alpha (TNFα) is considered to play a key role in the pathogenesis of intervertebral disc disease. To evaluate the importance of this cytokine we examined the inflammatory environment and spinal phenotype of 9-month-old human TNFα overexpressing transgenic (hTNFα-TG) mice. The mice evidenced increased circulating levels of interleukin-1β (IL-1β), IL-2, keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and monocyte chemoattractant protein-1 (MCP-1) along with thinning of the cortical and trabecular vertebral bone. Surprisingly, although the nucleus pulposus (NP) of these mice was intact and healthy, the caudal annulus fibrosus (AF) evidenced robust cell death and immune cell infiltration. Despite these differences, there were no obvious alterations in the collagen or aggrecan content in the NP and AF. However, there was a reduction in cartilage oligomeric matrix protein (COMP), suggesting destabilization of the AF matrix. Microarray analysis of the NP from hTNFα-TG mice cells revealed minimal changes in global gene expression. These findings lend support to the notion that NP tissue is isolated from systemic inflammation. In contrast, the severe AF phenotype suggests that systemic inflammation interferes with AF health, predisposing discs to herniation as opposed to directly causing NP degeneration. © 2020 American Society for Bone and Mineral Research.