Risk factor analysis of femoral avascular necrosis after operation for Tönnis grade IV developmental dysplasia of the hip.

PURPOSE: We explored the risk factors for avascular necrosis (AVN) after surgery using open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV developmental dysplasia of the hip (DDH). METHODS: In this retrospective study, we collected data of patients with Tönnis grade IV DDH treated with open reduction and pelvic osteotomy combined with femoral osteotomy from January 2012 to May 2020. The patients were divided into the AVN group and non-AVN group using the Kalamchi-MacEwen classification system. The clinical and imaging data of the two groups were collected, and the possible risk factors were included in the analysis. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors and odds ratios of AVN. RESULTS: In all, 254 patients (mean age; 2.6±0.9 years, 278 hips) were included. The mean follow-up time was 3.8±1.5 years. A total of 89 hips (32%) were finally classified as AVN (Kalamchi-MacEwen II-IV). Univariate analysis showed significant associations with AVN for age (p=0.006), preoperative femoral neck anteversion (FAV) (p<0.001), femoral osteotomy length to dislocation height ratio (FDR) <1 (p<0.001), and the epiphyseal ossific nucleus diameter to the neck diameter ratio (ENR) <50% (p=0.009). Multivariate logistic regression analysis showed that only excessive preoperative FAV (OR: 1.04; 95% CI: 1.02-1.05; p<0.001) and FDR<1 (OR: 3.58; 95% CI: 2.03-6.31; p<0.001) were independent risk factors for femoral head necrosis. CONCLUSION: Excessive preoperative FAV and FDR<1 are important risk factors for femoral AVN after open reduction, pelvic osteotomy, and femoral osteotomy for Tönnis grade IV DDH. For children with DDH with high dislocation and excessive FAV, clinicians should fully evaluate their condition and design more personalized treatment programs to prevent AVN.

Objective Sleep Duration and All-Cause Mortality Among People With Obstructive Sleep Apnea.

Importance: The association between sleep duration and all-cause mortality remains unclear among people with obstructive sleep apnea (OSA). Objective: To explore whether there is an association between sleep duration and all-cause mortality among people with OSA. Design, Setting, and Participants: This cohort study investigated participants with OSA from the Sleep Heart Health Study (SHHS) in which participants were enrolled between 1995 and 1998 with questionnaires and polysomnography (PSG) assessment and followed up for a median of 11.8 years. SHHS was a multicenter community-based study; 2574 participants with OSA defined by apnea-hypopnea index (AHI) greater than or equal to 15 from SHHS were found; all of them had all-cause mortality data and were included in the study. Data were analyzed from November 2022 to October 2023. Exposures: Participants were divided into 4 groups with objective sleep duration of (1) at least 7 hours, (2) 6 to less than 7 hours, (3) 5 to less than 6 hours, and (4) less than 5 hours, which was determined by total sleep time on PSG at baseline. Main Outcomes and Measures: All-cause mortality was defined as deaths from any cause and its risk was compared among 4 OSA groups using Cox regression models. Results: A total of 2574 participants with OSA were included (1628 [63.2%] men and 946 [36.8%] women; mean [SD] age, 65.4 [10.7] years; 211 [8.2%] Black, 2230 [86.6%] White, 133 [5.2%] other race). Overall, 688 all-cause deaths were observed in participants. Compared with the group sleeping at least 7 hours, the groups sleeping 6 to less than 7 hours (hazard ratio [HR], 1.53 [95% CI, 1.13-2.07]), 5 to less than 6 hours (HR, 1.40 [95% CI, 1.03-1.90]), and less than 5 hours (HR, 1.64 [95% CI, 1.20-2.24]) had significantly higher risks of all-cause mortality independent of AHI. Sensitivity analyses were performed among participants with available data of positive airway pressure treatment during follow-up and the finding was mostly consistent, albeit the HR for the group of 5 to less than 6 hours was not statistically significant. Conclusions and Relevance: In this cohort study of 2574 participants with OSA, those with shorter objective sleep duration had higher risk of all-cause mortality independent of AHI compared with those sleeping at least 7 hours. Further studies would be needed to investigate health benefits of extending sleep length among people with OSA with short sleep duration.

The impact of exosomes derived from distinct sources on rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of individuals. Exosomes, which are cellularly secreted vesicles, possess favorable biological traits such as biocompatibility, stability, and minimal toxicity. Additionally, they contain nucleic acids, lipids, proteins, amino acids, and metabolites, serving as mediators in cellular communication and information exchange. Recent studies have demonstrated the association between exosomes and the pathogenesis of RA. Exosomes derived from mesenchymal stem cells, dendritic cells, and neutrophils exert influence on the biological functions of immune cells and joint cells, however, the precise mechanism remains largely unclarified. This comprehensive review systematically analyzes and summarizes the biological characteristics and functionalities of exosomes derived from diverse cellular sources, thus establishing a scientific foundation for the utilization of exosomes as diagnostic targets and therapeutic modalities in the context of RA.

Interstitial lung disease in adult patients with anti-NXP2 antibody positivity: a multicentre 18-month follow-up study.

OBJECTIVES: Anti-nuclear matrix protein 2 (NXP2) antibody is a rare myositis-specific antibody. Thus, the pattern and prognosis of interstitial lung disease (ILD) in NXP2-positive patients remain unclear. This study investigates the clinical features and effects of pulmonary complications on survival in NXP2-positive patients. METHODS: We retrospectively analysed the clinical and follow-up data of a cohort of 33 hospitalised adult patients with anti-NXP2 antibody positivity at three tertiary rheumatology centres from June 2017 to December 2020. RESULTS: Thirty-three patients were enrolled, and 87.9% (29/33) had dermatomyositis. The major pulmonary lesions manifested as various types of ILD (14/33, 42.4%), bilateral pleural effusion (2/33, 6.1%) and diffuse alveolar haemorrhage (1/33, 3%). Only 3 patients (3/33, 9.1%) had respiratory symptoms at onset. The most common lung imaging manifestations were non-specific interstitial pneumonia (NSIP) and/or organising pneumonia (OP) (11/14, 78.6%). Patients in the ILD group were older than those in the non-ILD group (p=0.002). Logistic regression analysis showed that age (p=0.008) was the only independent predictor for ILD. Kaplan-Meier survival curves displayed no association between ILD and all-cause death (log-rank p=0.84). None of the deaths during follow-up were directly related to ILD. CONCLUSIONS: Adult patients with anti-NXP2 antibody positivity mainly had dermatomyositis. Concurrent ILD is not uncommon, but clinical manifestations are often latent. NSIP and/or OP are the most common patterns. ILD is more common in older age groups. Although the prognosis of patients in the ILD group is not very poor, early screening may help to improve prognosis and quality of life.

Collagen I in the Hip Capsule Plays a Role in Postoperative Clinical Function in Patients With Developmental Dysplasia of the Hip.

The aims of the present study is to evaluate the roles of collagen I and III in the hip capsule in the postoperative clinical function of patients with developmental dysplasia of the hip (DDH). Hip capsules from 155 hips of 120 patients were collected during surgery. The patients were divided into three groups according to age: I: 2-3.5 years; II: 3.5-5 years; and III: 5-6 years. Patient clinical function and radiographic outcomes were evaluated with the McKay scores and Severin classification. The expression of collagen I and III was detected through immunohistochemistry and quantitative reverse transcription polymerase chain reaction (RT-PCR) and analyzed according to age, sex, degree of dislocation and McKay classification. All patients received open reduction and pelvic osteotomy and/or femoral shortening osteotomy and achieved good results on the basis of postoperative X-ray imaging. The average follow-up time was 3.4 years (range 2-4.3 years). There were no changes in the expression of collagen III in the different groups. The expression of collagen I according to age and sex was not significantly different. Lower expression of collagen I was observed in DDH patients with a higher degree of dislocation according to the Tonnis grade. The highest expression of collagen I was detected in the group with poor clinical function according to the McKay classification. Collagen I is correlated with the degree of dislocation and is a risk factor for poor clinical function in DDH patients. Collagen I is correlated with the degree of hip dislocation and poor clinical function in DDH patients.

Application of deep-learning-based artificial intelligence in acetabular index measurement.

Objective: To construct an artificial intelligence system to measure acetabular index and evaluate its accuracy in clinical application. Methods: A total of 10,219 standard anteroposterior pelvic radiographs were collected retrospectively from April 2014 to December 2018 in our hospital. Of these, 9,219 radiographs were randomly selected to train and verify the system. The remaining 1,000 radiographs were used to compare the system's and the clinicians' measurement results. All plain pelvic films were labeled by an expert committee through PACS system based on a uniform standard to measure acetabular index. Subsequently, eight other clinicians independently measured the acetabular index from 200 randomly selected radiographs from the test radiographs. Bland-Altman test was used for consistency analysis between the system and clinician measurements. Results: The test set included 1,000 cases (2,000 hips). Compared with the expert committee measurement, the 95% limits of agreement (95% LOA) of the system was -4.02° to 3.45° (bias = -0.27°, P < 0.05). The acetabular index measured by the system within all age groups, including normal and abnormal groups, also showed good credibility according to the Bland-Altman principle. Comparison of the measurement evaluations by the system and eight clinicians vs. that of, the expert committee, the 95% LOA of the clinician with the smallest measurement error was -2.76° to 2.56° (bias = -0.10°, P = 0.126). The 95% LOA of the system was -0.93° to 2.86° (bias = -0.03°, P = 0.647). The 95% LOA of the clinician with the largest measurement error was -3.41° to 4.25° (bias = 0.42°, P < 0.05). The measurement error of the system was only greater than that of a senior clinician. Conclusion: The newly constructed artificial intelligence system could quickly and accurately measure the acetabular index of standard anteroposterior pelvic radiographs. There is good data consistency between the system in measuring standard anteroposterior pelvic radiographs. The accuracy of the system is closer to that of senior clinicians.

Age-related changes in expression of lysine48 and lysine63 ubiquitin linkages in dopamine neurons of midbrain in mice.

Ubiquitination of target proteins is mediated via different ubiquitin lysine (K) linkages and determines the protein fates. In particular, K48 ubiquitin linkage targets proteins for degradation, whereas K63 ubiquitin linkage plays a nondegradative role. Parkinson's disease is an age-onset neurodegenerative disorder, which shows selective loss of dopamine neurons in substantia nigra pars compacta (SNC) and ubiquitinated protein aggregates. However, age-related expression of K48 and K63 ubiquitin linkages in SNC dopamine neurons remains elusive. We thus sought to explore the expression of K48 and K63 ubiquitin linkages in dopamine neurons in SNCs of mice at different ages with morphological and biochemical assays. Here our results indicated that in 5-week-old mice, dopamine neurons presented higher levels of K48 and K63 ubiquitin linkages than nondopamine neural cells. Aging promoted the formation of protein aggregates that are positive for both K48 and K63 ubiquitin linkages, together with tyrosine hydroxylase, a dopamine neuron marker. Moreover, 21-month-old mice showed fewer neural cells and tyrosine hydroxylase positive neurons in the SNCs than younger mice. Through biochemical analysis, the 21-month-old mice were shown to express more K48 ubiquitin linkages and less tyrosine hydroxylase and NeuN than the 5-week-old mice. These results suggest the first time that expression of K48 and K63 ubiquitin lysine linkages in midbrain dopamine neurons is age-related and may be involved in the loss of dopamine neurons.

Gelatin promotes cell aggregation and pro-inflammatory cytokine production in PMA-stimulated U937 cells by augmenting endocytosis-autophagy pathway.

Gelatin, denatured collagen, temporarily exists in tissues and may well be pathophysiologically involved in tissue remodeling, inflammation or tissue damage. The present study is aimed to investigate possible biological roles of gelatin by examining its effects on monocyte-like histiocytic lymphoma cell line U937. Once stimulated by phorbol 12-myristate 13-acetate (PMA), U937 cells differentiate into macrophage-like cells, changing from non-adherent to adherent cells with extended pseudopodia. Here we pre-treated the cell dishes with gelatin solution for cell culture. Interestingly, we found that PMA-stimulated U937 cells formed multicellular aggregates on gelatin-coated dishes, accompanying NF-κB-mediated production of pro-inflammatory cytokines, whereas cell aggregation was not detected on non-coated dishes. Moreover, differentiated U937 cells on gelatin-coated dishes showed increased autophagy level and endocytosis. Surprisingly, formation of multicellular aggregates and pro-inflammatory cytokine production were both attenuated by either down-regulation of autophagy with inhibitors, such as 3-methyladenine (3MA) or chloroquine (CQ), or repression of endocytosis with siRNA targeting Endo180. Moreover, autophagy was inhibited by si-Endo180, and endocytosis was suppressed by 3MA, suggesting a positive feedback loop between autophagy and endocytosis. The results revealed that gelatin-coating induced differentiated U937 cells to form cell aggregates and promote NF-κB-mediated pro-inflammatory cytokine production at least partially through an endocytosis-autophagy pathway.

Superficial siderosis of the central nervous system induced by a single-episode of traumatic subarachnoid hemorrhage: a study using MRI-enhanced gradient echo T2 star-weighted angiography.

The purpose of this study was to examine whether a single episode of traumatic subarachnoid hemorrhage (tSAH) could cause superficial siderosis of the central nervous system (SS-CNS).This study was approved by the local ethics committee. Thirty-two patients with a history of a single episode of tSAH were enrolled in the study. An episode of tSAH was confirmed in patients based on a CT scan or a lumbar puncture, and a follow-up examination was conducted at least six weeks after the brain trauma. A follow-up MRI examination was performed, using enhanced gradient echo T2 star-weighted angiography (ESWAN) to detect hemosiderin deposition on the cortical surface. The extent to which hemosiderin deposition was associated with several clinical factors was investigated. Various degrees of hemosiderin deposition were detected in 31 of 32 (96.9%) single-episode tSAH patients. Analysis of contingency tables revealed an association between the regions of subarachnoid bleeding based on CT images and the regions of hemosiderin deposition based on ESWAN images (χ2 = 17.73, P<0.05). SS-CNS was determined to be a common consequence after a single episode of tSAH. The extent of hemosiderin deposition is closely correlated with the initial bleeding sites and bleeding volume.