Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury

Determining Accuracy of Chondral Lesion Sizing Methods Prior to Surgery

Background: Osteochondral lesions of the knee may require cartilage restoration such as osteochondral allograft (OCA) transplantation or autologous chondrocyte implantation (ACI). Although MRI and arthroscopy can offer valuable information regarding lesion characteristics prior to these procedures, no study has compared the use of each in estimating the sizes of grafts used at the time of surgical correction. Hypothesis/Purpose: To compare osteochondral defect size measurements and characteristics across MRI, arthroscopy, and at the time of implantation with OCA or ACI. Study Design: Retrospective Cohort Study (Level III) Methods: Patients who underwent ACI and OCA transplantation at a single institution between 2015 and 2019 were retrospectively identified. Osteochondral lesion characteristics including size were collected preoperatively from MRI and arthroscopy and at the time of definitive open surgical intervention. Subgroup analysis was performed comparing measurement techniques depending on the corrective surgical approach used as well as depending on the mechanism of chondral injury to determine if these had any effect on the ability of arthroscopy or MRI to predict graft size. Results: Overall, 136 chondral lesions were addressed with restoration procedures in 117 patients (mean age 32.5 years). Average difference between final graft size and lesion area measured with index arthroscopy was 116 mm2, while average difference between final graft size and lesion size measured with preoperative MRI was 182 mm2 (P \u3c .001). Depending on surgical technique, measurements with MRI were more similar to final graft size when a patient underwent OCA transplantation versus ACI (P = .007). Depending on mechanism of injury, MRI measurements of lesions were closer to graft area when lesions resulted from trauma (P = .047). Conclusion: Chondral lesion size determined by preoperative MRI imaging is less accurate than arthroscopic measurements. The mechanism injury leading to chondral damage and degree of damage may influence the ability of MRI and arthroscopy to accurately measure chondral lesions and predict the final graft size used in surgical correction. Future studies may be warranted to further investigate influencing factors that alter the reliability of arthroscopy and MRI in measuring chondral lesions. Magnetic Resonanc

Physical Examination Versus Ultrasonography for Detection of Ulnar Nerve Subluxation in Professional Baseball Pitchers

Background: Despite the importance of accurately detecting ulnar nerve subluxation in vulnerable athletes, few studies have compared the performance of physical examination and ultrasound in this population. Purpose/Hypothesis: The purpose of this study was to compare the diagnostic validity of physical examination versus ultrasound in detecting ulnar nerve subluxation at the cubital tunnel of the elbow in professional baseball pitchers. It was hypothesized that ultrasound would more sensitively detect ulnar nerve subluxation. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: Physical and sonographic examinations for ulnar nerve subluxation were performed on 186 elbows of 95 consecutive male professional baseball pitchers (age, 17-30 years) as a routine part of their spring training assessments. Provocative maneuvers consisting of the Tinel and elbow flexion-compression tests were evaluated over the cubital tunnel. The validity of physical examination for detecting ulnar nerve subluxation at the elbow was determined using ultrasonographic examination for comparison. Results: Ulnar nerve subluxation was detected by physical examination in 58 (31.2%) elbows and by ultrasonography in 61 (32.8%) elbows. Of the 58 elbows with positive physical examination, 47 were positive on ultrasound. Using a positive ultrasound as a reference, the accuracy of the physical examination was 86.6%, with 77% sensitivity and 91.2% specificity. The positive and negative predictive values of physical examination were 81% and 89.1%, respectively. There was no relationship between nerve instability and positive provocative tests overall, in dominant versus nondominant arms, or in right versus left arms (P \u3e.05 for all). Conclusion: Physical examination had moderate sensitivity and high specificity for detecting ulnar nerve subluxation at the cubital tunnel of the elbow when compared with ultrasound. These findings suggest that when detecting the presence of a subluxating ulnar nerve is most important, it may be advisable to obtain an ultrasound evaluation instead of relying on a physical examination; however, physical examination alone may be appropriate for ruling out subluxation

Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury