Citations

The reshaping of the immune system which occurs during aging has detrimental consequences for tissue function and pathology. The August 2025 issue of Nature Aging provides a Focus on immune aging, featuring a series of reviews and opinion pieces on recent advances in immune aging research. This panel discussion hosted by Nature Aging with experts in the field accompanies the Focus issue, and covers emerging concepts in immune aging as well as translational therapies.

Introduction: Pregnancy can be a complex and risk filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods: The GRADE process was used when sufficient published data were available and the RAND process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results: The topics were divided into 10 categories with 34 GRADE recommendations and 35 Consensus statements. Discussion: Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.

Abstract Objectives Effective communication is crucial in healthcare, and for patients with a non-English language preference (NELP), professional interpreters are recognized as the gold standard in supporting bidirectional communication. However, interpreters are not always readily available, prompting the exploration of other options for translation and interpretation. The recent developments in artificial intelligence-based neural network translation tools, namely neural machine translation (NMT) may enable robust interpretation and translation. Materials and Methods We conducted a systematic review (SR) to evaluate the literature on NMT for this purpose. We did a comprehensive search of several databases with guidance from a professional librarian. The search was limited to the year 2000 onwards and English language. Title and abstract screening and full-text review were independently conducted by two reviewers with conflicts resolved by a third reviewer Results 2867 studies were identified with 10 studies included in the final analysis. Among these, six evaluated interpretation in real or simulated clinical settings and four examined translation of discharge materials. Google Translate and ChatGPT were assessed in several studies. Accuracy differed by language, with low-resource languages performing worse. Discussion NMT technologies in healthcare have several advantages including broad language accessibility and potential cost savings for institutions. Despite improved accuracy of these novel tools, due to possible critical errors NMT tools are not yet ready for widespread clinical use. Conclusion Future studies should focus on optimizing evaluation methods as well as how best to integrate these technologies into real-time clinical settings.

ABSTRACT Background Idiopathic subglottic stenosis (iSGS) occasionally affects women of childbearing age. Surgical intervention is the primary treatment, yet limited research exists on factors influencing disease severity. This study explores the impact of hormonal contraception on iSGS recurrence rates and surgery‐free intervals. Methods This retrospective study was conducted at a tertiary academic care center. Patients using hormonal birth control (e.g., estrogen‐progesterone pills, progesterone implants) during their first procedure were classified in “Birth Control (BC)” group, while those not using contraceptives were placed in “No Birth Control (NBC)” group. Poisson regression evaluated recurrence rates, and Mann–Whitney tests assessed surgery‐free intervals. Kaplan–Meier analysis estimated time to first recurrence, adjusting for age and follow‐up duration. Results Twenty‐six patients were in the NBC group and 12 in the BC group (average ages 37 and 34, respectively). Patients in the NBC group were 2.6 times more likely to experience recurrence compared to those in the BC group ( p = 0.001). The expected number of recurrences for the BC group was 0.4 times that of the NBC group (95% CI: 0.2–0.7; p = 0.001). Furthermore, patients taking birth control were significantly less likely to have a first recurrence (HR: 0.4; 95% CI: 0.2–0.9; p = 0.025) and had longer times to first recurrence (Figure 1; p = 0.031). Conclusions Birth control appears to protect against iSGS severity, potentially through hormonal mechanisms. Hormonal contraception may serve as a non‐surgical alternative for managing iSGS. Future prospective studies may evaluate outcomes in newly diagnosed iSGS patients started on birth control compared to those not using hormonal contraceptives. Level of Evidence 3.

Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a critical pathway in the pathogenesis of ischemia–reperfusion-induced AKI (IR-AKI). Although sex differences in susceptibility to IR-AKI have been reported, it remains unclear whether there are sex differences in necroptosis dynamics and whether these differences underlie the observed sexual dimorphism in kidney IRI. This study aimed to address these questions. Methods: male and female C57BL/6 J mice were subjected to AKI via ischemia induced by bilateral renal pedicle clamping for 18 min at 37 °C. Plasma, urine, and kidney samples were collected at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-reperfusion. Kidney injury and function were assessed by measuring plasma creatinine (PCr), blood urea nitrogen (BUN) levels, and histological damage (PAS and cleaved caspase3 staining). Necroptosis activation was assessed by quantifying phosphorylated forms of key markers: p-RIPK1 and p-MLKL. To explore the role of sex hormones in regulating necroptosis dynamics, ovariectomized female mice were subjected to the same IR-AKI protocol, and their kidney injury and functional outcomes were compared with those of intact counterparts. Results: The PCr was 0.35 ± 0.04 and 0.32 ± 0.06 mg/dL for males and females, respectively, at 3 h of IR. The levels exponentially increased to 2.05 ± 0.18 at 48 h post-reperfusion in the males but only gradually to 0.94 ± 0.13 mg/dL in females. Necroptosis activation began as early as 3 h post-IR in males but was delayed until ~6 h in females. Males exhibited stronger and more sustained necroptosis activation than females, showing elevated phosphorylation levels of pRIPK1 and pMLKL in Western blot. Female sex hormone deficiency exacerbated the female response to IR-induced injury, which reduced the sex difference in the dynamic of the necroptotic activation and subsequent kidney injury. To our knowledge, this is the first study to characterize sex differences in the initiation and progression of necroptosis and subsequent injury in a mouse model of IR-AKI. Conclusions: Our findings reveal distinct temporal patterns of programmed cell death between sexes. Necroptosis-targeted therapies require early intervention in males, which can be delayed in females after IR-AKI, highlighting the need for sex-specific therapeutic windows.

Abstract Background The diagnosis of periprosthetic joint infection (PJI) is facilitated by consensus identification of synovial biomarkers, which may be aided by targeted microbial next generation sequencing (NGS) of synovial fluid. The primary objective of the study was to evaluate NGS performance across 3 years to ICM 2018 minor criteria for PJI. Methods Synovial fluid specimens submitted from 2020–2022 by outpatient surgical clinics to MicroGenDX for matched synovial biomarker and NGS analysis were selected for retrospective analysis. Synovial biomarkers tested included C-reactive protein (CRP), white blood cell (WBC) count, and polymorphonuclear (PMN) leukocyte percentage. Synovial fluid analysis compared NGS microbial positivity with positive incidence of PJI determined by scoring of synovial biomarkers using ICM 2018 minor criteria for infection. Results The overall sensitivity, specificity, and accuracy of NGS to ICM diagnosed PJI across 2,011 specimens was 76.4% [95% CI: 0.723–0.801], 92.3% [0.91–0.94], and 88.7% [0.87–0.90], respectively. When comparing the diagnostic performance of NGS and individual biomarkers to infection, NGS was more specific to PJI than synovial CRP (specificity = 0.894, 95% CI: 0.88–0.91), but not PMN or WBC. NGS was positive in 7.7% of ICM negative samples. NGS positive:ICM negative samples were associated with significantly elevated synovial PMN (p = 0.001) and WBC (p < 0.0001) compared to NGS negative:ICM negative samples. Across all samples, NGS positivity was associated with significantly elevated results for all tested biomarkers (p < 0.0001). Eight bacterial species dominated the composition in 68% of samples, whereas 46 different microbes were dominant in the remaining third. Conclusions Microbial targeted NGS positivity was concordant with ICM minor criteria for PJI and should be considered a useful tool for diagnosis. There is a low risk of false positive detections comparable to ICM biomarkers. Elevated biomarkers in NGS positive:ICM negative samples may indicate infection occurring that is poorly captured by the three measured synovial biomarkers. Uncommon species are collectively common to PJI and NGS is uniquely positioned to detect such species as they are frequently missed by conventional microbiological testing, including culture and quantitative PCR. These results suggest formal diagnostic schemes would benefit from the addition of NGS as a diagnostic criterion.

Background Patients are enrolled into hospice for a variety of conditions. There are few recent data on the differences of survival duration after hospice enrollment, particularly regarding age, sex, and reason for hospice admission. Methods Using previously obtained data, we calculated age at enrollment, reported sex, and classified patients into nine classes of hospice-qualifying conditions (HQC). We then applied Wilcoxon rank-sum analysis comparing median survival and the percent of patients surviving at least 6 months. Findings 53.38% of patients were female. The median age was 83.03 years. The median survival duration overall was 17.36 days (Inter-quartile range 5.35-62.08). Median survival was lowest for “Infectious” HQC (4.69d) and highest for “Other” (28.53d). Women survived longer than men (19.34 vs 15.37 days). Those older than median survived longer (20.51 days vs 15.03). Overall, 9.47% of enrollees survived at least 6 months. This was more common for women (10.99%), those older than 83 (12.44%), and those enrolled for dementia (16.46%). Discussion Relevant information of what can be expected after hospice enrollment is crucial for families and patients. These differences also indicate potential bias in assessment of hospice applicability, enrolling women, older patients, and patients with specific diagnoses earlier in their disease course.