AKI treated with kidney replacement therapy in critically Ill allogeneic hematopoietic stem cell transplant recipients.

Acute kidney injury (AKI) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but few studies have focused on AKI treated with kidney replacement therapy (AKI-KRT), particularly among critically ill patients. We investigated the incidence, risk factors, and 90-day mortality associated with AKI-KRT in 529 critically ill adult allo-HSCT recipients admitted to the ICU within 1-year post-transplant at two academic medical centers between 2011 and 2021. AKI-KRT occurred in 111 of the 529 patients (21.0%). Lower baseline eGFR, veno-occlusive disease, thrombotic microangiopathy, admission to an ICU within 90 days post-transplant, and receipt of invasive mechanical ventilation (IMV), total bilirubin ≥5.0 mg/dl, and arterial pH <7.40 on ICU admission were each associated with a higher risk of AKI-KRT. Of the 111 patients with AKI-KRT, 97 (87.4%) died within 90 days. Ninety-day mortality was 100% in each of the following subgroups: serum albumin ≤2.0 g/dl, total bilirubin ≥7.0 mg/dl, arterial pH ≤7.20, IMV with moderate-to-severe hypoxemia, and ≥3 vasopressors/inotropes at KRT initiation. AKI-KRT was associated with a 6.59-fold higher adjusted 90-day mortality in critically ill allo-HSCT vs. non-transplanted patients. Short-term mortality remains exceptionally high among critically ill allo-HSCT patients with AKI-KRT, highlighting the importance of multidisciplinary discussions prior to KRT initiation.

Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight.

Microphysiological systems provide the opportunity to model accelerated changes at the human tissue level in the extreme space environment. Spaceflight-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting in older adults, known as sarcopenia. These shared attributes provide a rationale for investigating molecular changes in muscle cells exposed to spaceflight that may mimic the underlying pathophysiology of sarcopenia. We report the results from three-dimensional myobundles derived from muscle biopsies from young and older adults, integrated into an autonomous CubeLab™, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analyses comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation. The analyses also revealed downregulated differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were downregulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides an approach to studying the cell autonomous effects of spaceflight on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. We also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLabTM payloads on the ISS.

Validation of Human Skeletal Muscle Tissue Chip Autonomous Platform to Model Age-Related Muscle Wasting in Microgravity.

Microgravity-induced muscle atrophy experienced by astronauts shares similar physiological changes to muscle wasting experienced by older adults, known as sarcopenia. These shared attributes provide a rationale for investigating microgravity-induced molecular changes in human bioengineered muscle cells that may also mimic the progressive underlying pathophysiology of sarcopenia. Here, we report the results of an experiment that incorporated three-dimensional myobundles derived from muscle biopsies from young and older adults, that were integrated into an autonomous CubeLabâ"¢, and flown to the International Space Station (ISS) aboard SpaceX CRS-21 in December 2020 as part of the NIH/NASA funded Tissue Chips in Space program. Global transcriptomic RNA-Seq analysis comparing the myobundles in space and on the ground revealed downregulation of shared transcripts related to myoblast proliferation and muscle differentiation for those in space. The analysis also revealed differentially expressed gene pathways related to muscle metabolism unique to myobundles derived from the older cohort exposed to the space environment compared to ground controls. Gene classes related to inflammatory pathways were uniquely modulated in flight samples cultured from the younger cohort compared to ground controls. Our muscle tissue chip platform provides a novel approach to studying the cell autonomous effects of microgravity on muscle cell biology that may not be appreciated on the whole organ or organism level and sets the stage for continued data collection from muscle tissue chip experimentation in microgravity. Thus, we also report on the challenges and opportunities for conducting autonomous tissue-on-chip CubeLab TM payloads on the ISS.