Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes.

Background: Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes.

A Mendelian randomization study finds no evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions.

This two-sample Mendelian randomization study examined causal associations of C-reactive protein (CRP) with spinal pain, the extent of multisite chronic pain, and chronic widespread musculoskeletal pain. No causal associations were found between CRP and these pain conditions.

Evaluating the representativeness of a cohort study of low back pain: Using electronic health record data to make direct comparisons of study participants with non-participants from the study population.

Representativeness is an important component of generalizability. Few studies have rigorously examined the representativeness of randomized trials or observational studies of pain or musculoskeletal conditions with regards to a wide range of factors beyond age, sex, race, and ethnicity. We conducted the first study of a pain condition that uses individual-level data to directly compare the enrolled study sample to the population from which it was drawn.

Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development.

Identification of biomarkers for COVID-19 associated secondary hemophagocytic lymphohistiocytosis.

Objectives: We aimed to define and validate novel biomarkers that could identify individuals with COVID-19 associated secondary hemophagocytic lymphohistiocytosis (sHLH) and to test whether fatalities due to COVID-19 in the presence of sHLH were associated with specific defects in the immune system.

Design: In two cohorts of adult patients presenting with COVID-19 in 2020 and 2021, clinical lab values and serum proteomics were assessed. Subjects identified as having sHLH were compared to those with COVID-19 without sHLH.

Acute kidney injury genetic risks: taking it 1 SNP at a time.

This commentary addresses some of the strengths, shortcomings, and challenges of the genome-wide association study of acute kidney injury (AKI) report in this issue. This AKI genome-wide association study is well executed and provides significant progress in finding 2 genome-wide significant loci. However, significant interpretive challenges remain, where advancements in methods are needed because of the clinical heterogeneity of the AKI phenotype, plus possible bias due to genetic correlation between index hospitalization risk and AKI risk.

No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study.

Objective: We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain.

Design: Two-sample MR study.

Setting/subjects: We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks.

PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome.

The relationship between the PD-L1 (Programmed Death-Ligand 1)/PD-1 pathway, lung inflammation, and clinical outcomes in acute respiratory distress syndrome (ARDS) is poorly understood. We sought to determine whether PD-L1/PD-1 in the lung or blood is associated with ARDS and associated severity. We measured soluble PD-L1 (sPD-L1) in plasma and lower respiratory tract samples (ARDS1 [ = 59] and ARDS2 [ = 78]) or plasma samples alone (ARDS3 [ = 149]) collected from subjects with ARDS and tested for associations with mortality using multiple regression.

Acute Kidney Injury, Systemic Inflammation, and Long-Term Cognitive Function: ASSESS-AKI.

Key Points: This study highlights that AKI is associated with long-term cognitive decline. Soluble TNF receptor 1 concentrations seem to mediate a significant proportion of the risk of long-term cognitive impairment after AKI.

Background: Cognitive dysfunction is a well-known complication of CKD, but it is less known whether cognitive decline occurs in survivors after AKI.

Identification of prognostic biomarkers for antibiotic associated nephrotoxicity in cystic fibrosis.

Background: Our objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation.

Methods: We populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19.

Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19.

Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies.

Importance: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies.

Objective: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies.

A dynamic in vitro developing testis model reflects structures and functions of testicular development in vivo.

To better define appropriate applications of our 3-dimensional testicular co-culture as a model for reproductive toxicology, we evaluated the ability of the model to capture structural and functional elements that can be targeted by reproductive toxicants. Testicular co-cultures were prepared from postnatal day 5 male rats and cultured with a Matrigel overlay. Following a 2-day acclimation period, we characterized functional pathway dynamics by evaluating morphology, protein expression, testosterone concentrations, and global gene expression at a range of timepoints from experimental days 0-21.

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.

Unlabelled: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.

Objectives: To assess the role of ANGPTL4 in COVID-19-related outcomes.

Alteration of oral microbiome composition in children living with pesticide-exposed farm workers.

Our prior work shows that azinphos-methyl pesticide exposure is associated with altered oral microbiomes in exposed farmworkers. Here we extend this analysis to show the same association pattern is also evident in their children. Oral buccal swab samples were analyzed at two time points, the apple thinning season in spring-summer 2005 for 78 children and 101 adults and the non-spray season in winter 2006 for 62 children and 82 adults.

Quantifying the phenome-wide disease burden of obesity using electronic health records and genomics.

Objective: High BMI is associated with many comorbidities and mortality. This study aimed to elucidate the overall clinical risk of obesity using a genome- and phenome-wide approach.

Methods: This study performed a phenome-wide association study of BMI using a clinical cohort of 736,726 adults.