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Shared multicellular injury programs of acute and chronic kidney disease enable mechanistic patient stratification
(medRxiv, 2026-03-06) Fallegger, Robin; Gomez-Ochoa, Sergio A.; Boys, Charlotte; Ramirez Flores, Ricardo Omar; Tanevski, Jovan; Pashos, Evanthia; Feliers, Denis; Piper, Mary; Schaub, Jennifer A.; Zhou, Zixiang; Mao, Weiguang; Chen, Xi; Sealfon, Rachel S. G.; Menon, Rajasree; Nair, Viji; Eddy, Sean; Alakwaa, Fadhl M.; Pyle, Laura; Choi, Ye Ji; Bjornstad, Petter; Alpers, Charles E.; Bitzer, Markus; Bomback, Andrew S.; Caramori, M. Luiza; Demeke, Dawit; Fogo, Agnes B.; Herlitz, Leal C.; Kiryluk, Krzysztof; Lash, James P.; Murugan, Raghavan; O'Toole, John F.; Palevsky, Paul M.; Parikh, Chirag R.; Rosas, Sylvia E.; Rosenberg, Avi Z.; Sedor, John R.; Vazquez, Miguel A.; Waikar, Sushrut S.; Wilson, F. Perry; Hodgin, Jeffrey B.; Barisoni, Laura; Himmelfarb, Jonathan; Jain, Sanjay; Ju, Wenjun; Troyanskaya, Olga G.; Kretzler, Matthias; Eadon, Michael T.; Saez-Rodriguez, Julio; Medicine, School of Medicine
Acute kidney injury (AKI) and chronic kidney disease (CKD) are two interconnected clinical conditions, both defined by degree of functional impairment, but with heterogeneous clinical trajectories. Using new transcriptomic technologies, recent studies have described the cellular diversity in the healthy and injured kidney at the single cell level. Here, we used single nucleus transcriptomics to investigate the molecular diversity and commonalities in kidney biopsies from over 150 participants with AKI and CKD enrolled within the Kidney Precision Medicine Project (KPMP) and did so at the patient participant level. Using an unsupervised approach, we identified two multi-cellular programs associated with clinical and histopathological features of acute injury and chronic damage, respectively. We found that these programs are expressed across patients with AKI and CKD, supporting shared, rather than distinct, underlying molecular mechanisms. These programs capture tissue-level compositional changes towards adaptive and failed-repair states in tubular epithelial cells, as well as intra-cellular molecular changes characteristic of stress in all cell types. We identified subunits of the NFkB and AP-1 complexes, as well as members of the STAT family, as putative upstream regulators of the acute and chronic programs. We were able to map these continuous molecular measures of acute injury and chronic damage to urine and plasma protein profiles obtained at time of biopsy. These non-invasive protein signatures were predictive of renal outcomes in an independent cohort of 44 thousand participants from the UK biobank. In summary, unbiased identification of cellular programs in kidney disease biopsies defined molecular programs of injury cutting across conventional disease categorization and established a non-invasive molecular link to long term patient outcomes.
Anaphylaxis Mimicking Severe Croup in Pediatric Patients: A Case Series
(Springer Nature, 2026-02-28) Putta Nagarajan, Hrithik Dakssesh; P. K., Roshan; Biswas, Md Ramij; Rameshkumar, Tejashvi; Baig, Mirza Adnan; Thirugnanasambandam, Nitish; Rameshkumar, Naveen Sundar; Medicine, School of Medicine
Acute stridor is frequently equated with croup in pediatric contexts; however, other conditions, such as anaphylaxis, may present with remarkably similar clinical and radiographic characteristics. This article presents two pediatric cases of acute stridor initially managed as croup but ultimately diagnosed and treated as anaphylaxis induced by seafood ingestion. Both patients experienced recovery following the administration of intramuscular adrenaline. These cases underscore the necessity for increased vigilance and comprehensive history-taking when evaluating pediatric acute stridor. Identifying allergic triggers and administering timely treatment can be lifesaving.
Knee health and associations with female-specific health, physical, psychological and social-gendered factors in women runners: the TRAIL-W cohort study protocol
(BMJ, 2026-03-11) Haberfield, Melissa J.; Mentiplay, Benjamin F.; De Oliveira Silva, Danilo; Hayman, Melanie; Dakic, Jodie; McGhee, Deirdre E.; Ryan-Atwood, Taliesin E.; Thornton, Jane S.; Clarke, Anthea; Govus, Andrew D.; Hill, Joshua P.; Cooper, Indiana; Serighelli, Fernanda; Patterson, Brooke; Bruder, Andrea; Girdwood, Michael A.; Carey, David; Tamer, Stephanie; Briggs, Connie; Schulz, Jenna; Trease, Lari; Johnston, Richard T. R.; West, Thomas J.; Warden, Stuart; Souza, Richard; Belski, Regina; Cooke, Matthew B.; Smith, Anne Julia; Binnie, Tara; Crossley, Kay M.; Physical Therapy, School of Health and Human Sciences
Introduction: Running is a popular recreational activity worldwide, with women's participation growing rapidly over the past decade. Compared with men, women runners are more likely to sustain a running-related injury, such as bone stress and knee injuries. Following a serious knee injury and subsequent surgery, women also experience worse knee and health-related outcomes than men. However, little is known about the intersection of female-specific health, physical, psychological and social-gendered factors with knee health in women runners with and without a history of knee surgery.
Methods and analysis: Building on the established 'TRAjectory of knee heaLth in runners' (TRAIL) prospective cohort study and designed with patient and content-expert partners, the nested TRAIL-W study will comprehensively explore the associations of multiple factors (ie, female-specific health, physical, psychological and social gendered) with knee health (symptoms and structural features), device-measured running load and running-related pain in women runners. Where appropriate, we will explore sex and/or gender differences. Alongside their scheduled TRAIL 6-monthly data collection, all active TRAIL female and male participants will be invited to complete a once-off 'TRAIL-W survey' and attend an additional laboratory-based assessment. The survey will include questionnaires measuring psychological, social gendered and, for women only, female-specific health factors. The laboratory assessment will measure body composition, bone mineral density and blood biomarkers. A subset of women will be invited to participate in qualitative interviews to understand women runners' experiences of female-specific health factors and their association with running behaviour.
Ethics and dissemination: Findings from TRAIL-W, approved by the La Trobe University Human Ethics Committee, will address critical research gaps by describing and exploring the diverse factors that may influence women runners' knee health.
The Impact of Surgical Non-Technical Skills on Clinical Outcomes: A Systematic Review
(Oxford University Press, 2025) Norton, Joel; Janda, Allison M.; Howie, Emma; Pohl, Nicole; Abahuje, Egide; Harrington, Steven D.; Popov, Vitaliy; Bauer, Tyler M.; Borges, Paulo; Roca, Gabriela Querejeta; Mathis, Michael R.; Strobel, Raymond J.; Airhart, Austin; Pham, Nicole; Harari, Ryan; Awtry, Jake A.; Pagani, Francis D.; Dias, Roger D.; Likosky, Donald S.; Yule, Steven; Video Assessment of CaRdiac Surgery QualITY (VARSITY) Surgery group; Surgery, School of Medicine
Background: Deficiencies in non-technical skills (NTS) such as leadership and communication can lead to intraoperative inefficiency and error. However, the relationship between these skills and patient-level outcomes has yet to be synthesized. The aim of this study was to systematically review the evidence examining the relationship between intraoperative NTS and clinical outcomes.
Methods: The PubMed, Embase, CENTRAL, CINAHL, and PsycINFO databases were searched for relevant studies published between inception and 1 November 2024. Eligible studies assessed NTS of operating room personnel, were conducted in non-simulated environments, and reported clinical outcomes. NTS were categorized into five core domains including leadership and communication. Patient-level outcomes comprised eight clinical measures including mortality and postoperative complications.
Results: Of 6313 screened studies, 21 met the inclusion criteria. Included studies represented 8536 participants performing 251 180 procedures across 13 specialties. Eleven observational studies assessed NTS of surgical personnel via study participants or observers. Ten interventional studies introduced NTS team training initiatives. Twelve of 21 studies (57%) incorporating 247 036 of all procedures (98.4%) reported significant improvements in clinical outcomes. Nine of 11 observational studies (82%) reported significant improvement in clinical outcomes compared with 3 of 10 interventional studies (30%). No studies demonstrated a significant deterioration in clinical outcomes associated with improved NTS.
Conclusion: Published evidence shows a significant link between intraoperative NTS and patient-level outcomes. These findings reinforce the value of behavioural assessment in surgery, support evidence-based team training, and underscore the need to embed NTS into regulatory frameworks to improve surgical quality and safety worldwide.
Comparison of Six Data Cleaning Methods for Determining Repetitive Head Impact Exposure in Youth Tackle Football
(Springer, 2026-01-23) DeAngelo, Samantha; Culiver, Adam; Le Flao, Enora; Shoaf, Nick; Doshi, Durshil; Tracy, Ryan; Aryeetey, Nii-Ayi; Quatrale, Anna; Smith, Carly; Ma, Jianing; Pan, Jeff; Yang, Jingzhen; Rose, Sean C.; Onate, James; Edwards, Nathan; Saygin, Zeynep; Caccese, Jaclyn B.; Physical Therapy, School of Health and Human Sciences
Purpose: Instrumented mouthguards (iMGs) are commonly used to quantify head acceleration event (HAE) exposure, but accurate interpretation requires rigorous data cleaning methods. This study compared six data cleaning methods for determining HAE rates and magnitudes, as well as cleaning method validity compared to the 5th method video verification in youth tackle football.
Methods: Fifty athletes (ages 8-12) wore Impact Monitoring Mouthguards during games across one season. Six data cleaning methods were applied to HAEs, including uncleaned data, time-windowing, proprietary classification algorithms, video verification, and combinations thereof. Impact rate, peak linear acceleration (PLA), and peak rotational velocity (PRV) were compared across methods using rate ratios, and intra-class correlation coefficients (ICCs), and non-parametric analyses.
Results: Data cleaning methods significantly influenced HAE rate but had minimal effect on magnitude. The uncleaned dataset produced the highest HAE rate (67.75 per athlete exposure), while the most stringent method (i.e., time-windowed, proprietary algorithm-classified, video-verified data) yielded the lowest (0.70 per athlete exposure). Although the time-windowed, proprietary algorithm-classified data demonstrated high specificity (0.96), it demonstrated low sensitivity (0.37) and positive predictive value (0.39) when compared to video-verified data. Differences in PLA across methods were not significant; only one significant difference in PRV was observed.
Conclusions: These findings highlight the impact of data cleaning on HAE quantification in youth tackle football. Although video verification remains best practice, it is resource intensive. Time-windowed, algorithm-classified data may serve as an efficient proxy in similar cohorts, though researchers should recognize its limitations. Findings support the need for standardized data cleaning methods and transparent reporting to ensure accurate and comparable HAE exposure estimates.