Replenishing IRAK-M expression in retinal pigment epithelium attenuates outer retinal degeneration.

Chronic inflammation is a constitutive component of many age-related diseases, including age-related macular degeneration (AMD). Here, we identified interleukin-1 receptor-associated kinase M (IRAK-M) as a key immunoregulator in retinal pigment epithelium (RPE) that declines during the aging process. Rare genetic variants of IRAK3, which encodes IRAK-M, were associated with an increased likelihood of developing AMD. In human samples and mouse models, IRAK-M abundance in the RPE declined with advancing age or exposure to oxidative stress and was further reduced in AMD. Irak3-knockout mice exhibited an increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M led to a disruption in RPE cell homeostasis, characterized by compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of adeno-associated virus (AAV)-expressing human IRAK3 rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in Irak3-knockout mice. Our data show that replenishment of IRAK-M in the RPE may redress dysregulated pro-inflammatory processes in AMD, suggesting a potential treatment for retinal degeneration.

Replenishing Age-Related Decline of IRAK-M Expression in Retinal Pigment Epithelium Attenuates Outer Retinal Degeneration.

Unchecked, chronic inflammation is a constitutive component of age-related diseases, including age-related macular degeneration (AMD). Here we identified interleukin-1 receptor-associated kinase (IRAK)-M as a key immunoregulator in retinal pigment epithelium (RPE) that declines with age. Rare genetic variants of IRAK-M increased the likelihood of AMD. IRAK-M expression in RPE declined with age or oxidative stress and was further reduced in AMD. IRAK-M-deficient mice exhibited increased incidence of outer retinal degeneration at earlier ages, which was further exacerbated by oxidative stressors. The absence of IRAK-M disrupted RPE cell homeostasis, including compromised mitochondrial function, cellular senescence, and aberrant cytokine production. IRAK-M overexpression protected RPE cells against oxidative or immune stressors. Subretinal delivery of AAV-expressing IRAK-M rescued light-induced outer retinal degeneration in wild-type mice and attenuated age-related spontaneous retinal degeneration in IRAK-M-deficient mice. Our data support that replenishment of IRAK-M expression may redress dysregulated pro-inflammatory processes in AMD, thereby treating degeneration.

The Iatrogenic Injury Potential of Self-adherent Elastic Bandages in Finger Injuries.

BACKGROUND: The use of a self-adherent, elastic bandage is a practical way to dress finger injuries. Multiple reports describe iatrogenic injuries from elastic bandages, ranging from skin necrosis to finger gangrene, necessitating amputations. This study investigated whether elastic bandages can compromise digital perfusion by occluding arterial blood flow in healthy volunteers and evaluated the utility of pulse oximetry as a monitoring tool for digital perfusion. A technique for safe bandage application is proposed. METHODS: A commercially available elastic bandage was wrapped around the index finger of 20 healthy volunteers at varying degrees of stretch. Digital perfusion measurements were carried out using photoelectric pulse transduction, laser Doppler flowmetry, and pulse oximetry. Intracompartmental pressure measurements were recorded using a separate in vitro experimental model. RESULTS: Elastic bandages applied at maximum stretch did not change digital brachial index or pulse oximetry values, suggesting arterial blood flow was preserved distal to the bandage. Intracompartmental pressure measurements at maximum stretch remained below the systolic digital pressure. In contrast, superficial dermal perfusion fell to 32% of normal as measured by laser Doppler flow, at 100% bandage stretch. CONCLUSION: This study suggests a risk for iatrogenic injury when using elastic bandages for finger dressings. While arterial inflow was never compromised, pressures were high enough to occlude superficial venous outflow, which may begin at 20% bandage stretch. Pulse oximetry failed to detect changes distal to applied dressings, and we do not recommend it to detect digital vascular compromise in this setting.

Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate.

The effect of using donation after circulatory death (DCD) hearts on waitlist outcomes has not been substantiated. We retrospectively analyzed 184 heart transplant (HT) candidates at our institution from 2019 to 2021. Patients were stratified into 2 observation periods centered on September 12, 2020, when the adult DCD HT program officially began. The primary outcome was a comparison of transplant rate between period 1 (pre-DCD) and period 2 (post-DCD). Secondary outcomes included waitlist time-to-transplant, waitlist mortality rate, independent predictors of incidence of HT, and posttransplant outcomes. A total of 165 HTs (n = 92 in period 1 and n = 73 in period 2) were performed. The median waitlist time-to-transplant decreased from 47.5 to 19 days in periods 1 and 2, respectively (P = .004). The transplant rate increased from 181 per 100 patient-years in period 1 to 579 per 100 patient-years in period 2 (incidence rate ratio, 1.87; 95% CI, 1.04-3.38; P = .038). There were no statistical differences in waitlist mortality rate (P = .566) and 1-year survival (P = .699) between the 2 periods. DCD HTs (n = 36) contributed to 49.3% of overall HT activity in period 2. We concluded that utilization of DCD hearts significantly reduced waitlist time and increased transplant rate. Short-term posttransplant outcomes were comparable between the pre-DCD and post-DCD periods.

Can EOS Imaging Substitute for Conventional Radiography in Measurement of Acetabular Morphology in the Young Dysplastic Hip?

BACKGROUND: EOS imaging offers a low-radiation alternative to conventional radiography (CR) and has little to no magnification effects. However, it is unclear how radiographic measures may be affected using EOS. The present study aims to determine the reproducibility of measures of acetabular morphology on EOS images as compared with CR, and to directly compare the 2 imaging modalities. METHODS: A total of 21 consecutive patients (66.7% female; 14.4±4.7 y) indicated for an open hip preservation procedure with both an anterior-posterior pelvis radiograph and EOS image performed preoperatively were included. Three orthopaedic surgeons measured Tönnis angle, lateral center edge angle (LCEA), acetabular depth-width ratio (ADR), and extrusion index (EI). Measurements were performed twice, 2 weeks apart. Reliability between observers and time points was measured using intraclass correlation coefficients, and agreement between time points and modalities was measured using Bland-Altman analysis. RESULTS: On EOS images, inter-rater reliability was 0.86 for Tönnis angle, 0.86 for LCEA, 0.74 for ADR, and 0.93 for EI. On CR, inter-rater reliability was 0.86 for Tönnis anlge, 0.90 for LCEA, 0.82 for ADR, and 0.84 for EI. In the agreement analysis, biases between imaging modalities were observed. On average, raters measured Tönnis angle and EI higher on EOS images than CR (2.22 degrees, 1.09%, respectively); and LCEA and ADR lower on EOS images than CR (1.54 degrees, 1.14% respectively). Limits of agreement (LOA) between modalities were similar to that of LOA observed in intra-rater analysis. CONCLUSIONS: Measures of acetabular morphology performed on EOS images have similarly high intra-rater and inter-rater reliability compared with CR. Measures performed on EOS also have similar intra-rater agreement as compared with CR. Intermodality agreement had similar LOA as intra-rater agreement on either individual imaging modality. Small biases between imaging modalities were detected. LEVELS OF EVIDENCE: Level I-diagnostic study: investigating a diagnostic test.