Citations

Background: When operative treatment is indicated, tibial spine fractures can be successfully managed with open or arthroscopic reduction and internal fixation (ARIF). The purpose of the study is to evaluate short-term treatment outcomes of tibial spine fractures in patients treated with both open and arthroscopic fracture reduction. Methods: We performed an Institutional Review Board (IRB)-approved retrospective cohort study of pediatric tibial spine fractures presenting between January 1, 2000 and January 31, 2019 at 10 institutions. Patients were categorized into 2 cohorts based on treatment: ARIF and open reduction and internal fixation (ORIF). Short-term surgical outcomes, the incidence of concomitant injuries, and surgeon demographics were compared between groups. Results: There were 477 patients with tibial spine fractures who met inclusion criteria, 420 of whom (88.1%) were treated with ARIF, while 57 (11.9%) were treated with ORIF. Average follow-up was 1.12 years. Patients treated with ARIF were more likely to have an identified concomitant injury (41.4%) compared with those treated with ORIF (24.6%, P=0.021). Most concomitant injuries (74.5%) were treated with intervention. The most common treatment complications included arthrofibrosis (6.9% in ARIF patients, 7.0% in ORIF patients, P=1.00) and subsequent anterior cruciate ligament injury (2.1% in ARIF patients and 3.5% in ORIF, P=0.86). The rate of short-term complications, return to the operating room, and failure to return to full range of motion were similar between treatment groups. Twenty surgeons with sports subspecialty training completed 85.0% of ARIF cases; the remaining 15.0% were performed by 12 surgeons without additional sports training. The majority (56.1%) of ORIF cases were completed by 14 surgeons without sports subspecialty training. Conclusion: This study demonstrated no difference in outcomes or nonunion following ARIF or ORIF, with a significantly higher rate of concomitant injuries identified in patients treated with ARIF. The majority of identified concomitant injuries were treated with surgical intervention. Extensive surgical evaluation or pretreatment magnetic resonance imaging should be considered in the workup of tibial spine fractures to increase concomitant injury identification. Level of Evidence: Level III.

The fibrogenic wound-healing response in liver increases stiffness. Here, macro and microheterogeneity of liver stiffness correlate with HSC heterogeneity in a hepatic fibrosis mouse model. Fibrogenic HSCs localized in stiff collagen-high areas upregulate the expression of focal adhesion molecule FHL2, which, in turn, promotes extracellular matrix protein expression. These results demonstrate that stiffness heterogeneity at the whole organ, lobular, and cellular level drives an amplification loop of fibrogenesis through specific focal adhesion molecular pathways.

AbstractAlthough Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA‐seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding β‐hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.

Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection has recently increased in incidence. Here, RNA-Seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. 227 genes with outlier expression were found (164 up-regulated and 63 down-regulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding beta-hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a useful resource for the identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns—a woman’s left and right breasts. From 341 features, we identified “robust” features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

Abstract Background and Aims Although magnetic resonance elastography (MRE) has been well‐established for detecting and staging liver fibrosis, its prognostic role in determining outcomes of chronic liver disease (CLD) is mostly unknown. Approach and Results This retrospective study consisted of 1269 subjects who underwent MRE between 2007 and 2009 and followed up until death or last known clinical encounter or end of study period. Charts were reviewed for cirrhosis development, decompensation, and transplant or death. The cohort was split into baseline noncirrhosis (group 1), compensated cirrhosis (group 2), and decompensated cirrhosis (group 3). Cox‐regression analysis with age, sex, splenomegaly, CLD etiology, Child‐Pugh Score (CPS), Fibrosis‐4 Index (FIB‐4) score, and Model for End‐Stage Liver Disease (MELD)–adjusted HR for every 1‐kPa increase in liver stiffness measurement (LSM) were used to assess the predictive performance of MRE on outcomes. Group 1 ( n = 821) had baseline median LSM of 2.8 kPa, and cirrhosis developed in 72 (8.8%) subjects with an overall rate of about 1% cirrhosis/year. Baseline LSM predicted the future cirrhosis with multivariable adjusted HR of 2.38 ( p < 0.0001) (concordance, 0.84). In group 2 ( n = 277) with baseline median LSM of 5.7 kPa, 83 (30%) subjects developed decompensation. Baseline LSM predicted the future decompensation in cirrhosis with FIB‐4 and MELD‐adjusted HR of 1.22 ( p < 0.0001) (concordance, 0.75). In group 3 ( n = 171) with median baseline LSM of 6.8 kPa (5.2, 8.4), 113 (66%) subjects had either death or transplant. Baseline LSM predicted the future transplant or death with HR of 1.11 ( p = 0.013) (concordance 0.53) but not in CPS and MELD‐adjusted models ( p = 0.08). Conclusion MRE‐based LSM is independently predictive of development of future cirrhosis and decompensation, and has predictive value in future transplant/death in patients with CLD.

Abstract Background Magnetic resonance imaging (MRI) and MRI‐based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol‐associated liver disease (ALD). Methods We utilized four different preclinical mouse models in our study: Model 1—mice were fed a fast‐food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2—mice were fed chronic‐binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin‐22 at different time points to induce disease regression; Model 3—mice were administered CCl 4 for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4—mice were administered EtOH plus CCl 4 for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions. Results Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three‐parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression ( r = 0.84, p < 0.0001) and regression ( r = 0.79, p < 0.0001) as measured by collagen content in livers. Conclusion This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.

Sweat out the fat with TSLP! Thymic stromal lymphopoietin (TSLP) is a cytokine that can promote immune responses that characterize allergic diseases. Choa et al . found that mice engineered to produce elevated TSLP displayed selective white adipose tissue loss that protected them from obesity, insulin resistance, and steatohepatitis (see the Perspective by Schneider). Protection was not mediated by eosinophils, regulatory T cells, or innate lymphoid cells. Rather, TLSP induced the migration of conventional T cells to sebaceous glands in the skin. Once there, these T cells promoted white adipose tissue loss by the hypersecretion of sebum, a lipid-rich substance that augments the skin’s barrier function. This mechanism, which likely evolved to enhance cutaneous antimicrobial defenses, could be possibly targeted in future treatments for obesity. —STS

AbstractAcute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID‐19) and is associated with in‐hospital death. We investigated the incidence of AKI in 223 hospitalized COVID‐19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID‐19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID‐19 and 99 with severe COVID‐19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID‐19 and 4.0% for moderate COVID‐19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150–8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361–13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622–22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 10⁹/L, interquartile range [IQR] 11.3 vs. 8.3 × 10⁹/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID‐19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID‐19 patients.