Risk factors of developmental dysplasia of the hip in infants: A meta-analysis based on cohort studies.

INTRODUCTION: Developmental dysplasia of the hip (DDH) is a prevalent condition in children. Currently, the exact etiology of DDH remains uncertain. The objective of this study was to conduct a meta-analysis to investigate the risk factors associated with DDH in infants. The findings would provide a theoretical foundation for targeted early screening and diagnosis. HYPOTHESIS: Several indicators, such as gender, intrauterine position, family history of DDH, gestational age, delivery mode, amniotic fluid levels, swaddling, parity, fetus number, combined musculoskeletal deformities, birth weight, and physical examination results, may serve as risk factors for DDH. MATERIALS AND METHODS: Cohort studies investigating the risk factors of DDH in infants through logistic regression analysis were searched in the Wanfang, VIP citation, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, Excerpta Medica Database (Embase), PubMed, and Cochrane Library databases up to May 2023. After extracting the data from eligible literature and assessing them using the Newcastle-Ottawa Scale (NOS), articles were selected based on pre-established inclusion and exclusion criteria. RESULTS: A total of eleven literature reports covering 979,757 infants were included in this meta-analysis. The publication bias did not significantly influence the results. The incidence rate of DDH was 47.99‰ among infants with risk factors compared to 3.21‰ in the general population. Risk factors for DDH included being female (OR=6.97, 95% CI: 5.18-9.39, p<0.001), breech delivery (OR=4.14, 95% CI: 3.09-5.54, p<0.001), positive family history (OR=4.07, 95% CI: 2.20-7.52, p<0.001), cesarean section (OR=1.11, 95% CI: 1.01-1.21, p=0.032), oligohydramnios (OR=3.93, 95% CI: 1.29-12.01, p=0.016), swaddling (OR=6.74, 95% CI: 1.25-36.31, p=0.026), firstborn status (OR=1.84, 95% CI: 1.49-2.53, p<0.001), combined musculoskeletal malformations (OR=2.27, 95% CI: 1.58-3.27, p<0.001), and physical signs of DDH (OR=8.71, 95% CI: 2.44-31.07, p=0.001). Premature delivery (OR=0.91, 95% CI: 0.88-0.95, p<0.001) was a protective factor for DDH. The relationship between multiple pregnancies (OR=0.58, 95% CI: 0.33-1.02, p=0.060) and low birth weight (OR=0.62, 95% CI: 0.14-2.76, p=0.529) in relation to DDH remained uncertain. DISCUSSION: This meta-analysis shows that female, breech delivery, positive family history, cesarean section, firstborn status, oligohydramnios, swaddling and combined musculoskeletal malformations are associated with DDH. Premature delivery appeared to be a protective factor against DDH. Nevertheless, the other factors need more research to reach more conclusive results. LEVEL OF EVIDENCE: III; meta-analysis.

A Stan tutorial on Bayesian IRTree models: Conventional models and explanatory extension.

IRTree models have been receiving increasing attention. However, to date, there are limited sources that provide a systematic introduction to Bayesian modeling techniques using modern probabilistic programming frameworks for the implementation of IRTree models. To facilitate the research and application of IRTree models, this paper introduces how to perform two families of Bayesian IRTree models (i.e., response tree models and latent tree models) in Stan and how to extend them in an explanatory way. Some suggestions on executing Stan codes and checking convergence are also provided. An empirical study based on the Oxford Achieving Resilience during COVID-19 data was conducted as an example to further illustrate how to apply Bayesian IRTree models to address research questions. Finally, strengths and future directions are discussed.

Submuscular plating vs. elastic stable intramedullary nailing for diaphyseal femur fractures in children: a systematic review and meta-analysis.

Objectives: This review evaluates the safety and efficacy of submuscular plating (SMP) vs. elastic stable intramedullary nailing (ESIN) in the treatment of pediatric femur shaft fracture. Method: Studies comparing the efficacy and safety of SMP and ESIN in pediatric shaft fracture were retrieved from five databases (PubMed, Embase, Cochrane, OVID, and Web of Science) from inception to March 2023 using a systematic literature search strategy. A total of 13 outcome measures, such as perioperative parameters, clinical outcomes, and radiographic results, were included in the meta-analysis. Results: Eight eligible studies involving 491 patients were included in the narrative synthesis. There were no significant differences in baseline characteristics between the two groups. Meta-analysis showed reduced radiation time (RT), soft tissue irritation and angular deformation in the SMP group than in the ESIN group. However, the SMP group had greater estimated blood loss (EBL) than the ESIN group. The duration of surgery, length of hospital stay (LOS), implant removal, complications requiring surgery, Flynn score, incidence of infection, fracture healing time, and limb length discrepancy (LLD) were similar between the two groups. Only one study reported higher incidences of fracture nonunion or delayed healing in the ESIN group. Conclusion: SMP is an effective and safe intervention superior to ESIN in reducing soft tissue irritation, angular deformation and radiation time. Given the presence of potential bias and heterogeneity, surgeons should select the treatment that would provide the best outcomes for EBL, LOS, operation time, and bone nonunion or delayed healing based on their experience. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023404118, Identifier PROSPERO (CRD42021228512).

Evaluation of open reduction of distal humerus fractures in children after implementation of an enhanced recovery after surgery program.

OBJECTIVE: This study assessed whether an enhanced recovery after surgery (ERAS) protocol could be beneficial for children with distal humerus fractures. METHODS: Children with distal humerus fractures (n = 85) were randomly assigned to the ERAS and control groups and subjected to different perioperative managements. This was followed by the evaluation of their intraoperative characteristics (operation time and bleeding), postoperative characteristics (food intake conditions, pain scores, and discharge time), and postoperative functions. RESULTS: The operation time, intraoperative bleeding, and postoperative hematological indices did not differ significantly between the two groups. Preoperative thirst and hunger were considerably less and the initial food intake duration following surgery was markedly shorter in the ERAS group than in the control group, whereas no difference between the groups was observed in the incidences of postoperative nausea and vomiting. A markedly reduced highest postoperative pain score and reduced mean pain score and demand for additional analgesic interventions were observed in the ERAS group compared with those in the control group, although the differences were not statistically significant. No noticeable between-group differences were observed in the incidences of postoperative incision problems, aspirational pneumonia, and gastroesophageal reflux. The total length of hospital stay was not significantly different between the two groups. However, the length of postoperative hospital stay was remarkably shorter and the elbow joint function at 2 months after surgery was significantly improved in the ERAS group compared with those in the control group. CONCLUSION: The ERAS protocol can ameliorate preoperative discomfort and postoperative pain, shorten the postoperative hospital stay, and accelerate postoperative functional recovery without increasing the risks of postoperative nausea, vomiting, and poor incision healing and is, therefore, worthy of clinical application.

Predictors for survival in patients with bone metastasis of small cell lung cancer: A population-based study.

ABSTRACT: The objective of the current study is to analyze the clinical and demographic characteristics of patients with bone metastasis of small cell lung cancer (SCLC) and explore their survival predictors.We retrospectively extracted patients with bone metastasis of SCLC from the Surveillance, Epidemiology, and End Results database. We applied Cox regression analyses to identify independent survival predictor of overall survival (OS) and cancer-specific survival (CSS). Only significant predictors from univariable analysis were included for multivariable Cox analysis. Kaplan-Meier method was used to evaluate survival differences between groups by the log-rank test.A total of 5120 patients with bone metastasis of SCLC were identified and included for survival analysis. The 1-year OS and CSS rates of bone metastasis of SCLC were 19.8% and 21.4%, respectively. On multivariable analysis, gender, age, radiotherapy, chemotherapy, liver metastasis, brain metastasis, insurance status, and marital status independently predicted OS and CSS. There was no significant difference of OS and CSS in terms of race and tumor size.Independent predictors of survival were identified among patients with bone metastasis of SCLC, which could be valuable to clinicians in treatment decision. Patients with bone metastasis of SCLC may benefit from radiotherapy and chemotherapy.

Treatment of pediatric femoral shaft fractures with elastic stable intramedullary nails versus external fixation: A meta-analysis.

BACKGROUND: There is currently a debate about whether elastic stable intramedullary nails (ESIN) or external fixation (EF) is the best surgical method for treating pediatric femoral shaft fractures. We performed a meta-analysis to determine which surgical method leads to higher treatment satisfaction, lower complication rates, and reduced treatment time, to investigate whether ESIN is the preferred surgical method for treatment of pediatric femoral shaft fractures. PATIENTS AND METHODS: Relevant databases were searched for comparative studies of ESIN versus EF for the treating pediatric femoral shaft fractures. Literature reports and quality evaluations were extracted, followed by a systematic review using RevMan 5.3 software. Treatment satisfaction at the last follow-up, primary complications, secondary complications, and relevant time indicators (operation time, hospital stay, clinical healing time, bone healing time) were analyzed. RESULTS: A total of 22 reports were included in this meta-analysis. We found no statistical differences in the treatment satisfaction at the last follow-up between ESIN and EF for the treatment of pediatric femoral shaft fractures. A low rate of postoperative re-fracture (RR=3.58, 95% CI (1.85, 6.92), p=0.0001) and postoperative infection (RR=9.25, 95% CI (5.32, 16.11), p<0.00001), and a high risk of skin irritation (RR=0.15, 95% CI (0.06, 0.37), p<0.00001) were found in the ESIN group. No significant differences between the two approaches were found regarding malunion. A low rate of limb-length discrepancy (RR=2.41, 95% CI (1.40, 4.17), p=0.002), hospitalization (SMD=0.84, 95% CI (0.24, 1.43), p=0.006), clinical healing time (SMD=0.95, 95% CI (0.56, 1.33), p<0.00001) and bone healing time (SMD=0.89, 95% CI (0.39, 1.40), p=0.005) were found in the ESIN group, as compared to that in the EF group. No significant differences were found in fixation failure, activity limitation of the joint, and operation time between the two strategies. DISCUSSION: ESIN should be the primary choice for the treatment of pediatric femoral shaft fractures since it has a reliable curative effect and results in a shorter hospital stay, faster fracture healing, and fewer complications. EF is recommended for fractures with serious injury of the soft tissue to avoid intramedullary infection. Double-blind high-quality randomized studies with larger sample sizes are warranted to confirm our conclusions. LEVEL OF EVIDENCE: IV.

Development and Validation of a Prognostic Nomogram for Extremity Soft Tissue Leiomyosarcoma.

Background: Extremity soft tissue leiomyosarcoma (LMS) is a rare disease with a poor prognosis. The aim of this study is to develop nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with extremity soft tissue LMS. Methods: Based on the Surveillance, Epidemiology, and End Results (SEER) database, 1,528 cases of extremity soft tissue LMS diagnosed between 1983 and 2015 were included. Cox proportional hazards regression modeling was used to analyze prognosis and obtain independent predictors. The independent predictors were integrated to develop nomograms predicting 5- and 10-year OS and CSS. Nomogram performance was evaluated by a concordance index (C-index) and calibration plots using R software version 3.5.0. Results: Multivariate analysis revealed that age ≥60 years, high tumor grade, distant metastasis, tumor size ≥5 cm, and lack of surgery were significantly associated with decreased OS and CSS. These five predictors were used to construct nomograms for predicting 5- and 10-year OS and CSS. Internal and external calibration plots for the probability of 5- and 10-year OS and CSS showed excellent agreement between nomogram prediction and observed outcomes. The C-index values for internal validation of OS and CSS prediction were 0.776 (95% CI 0.752-0.801) and 0.835 (95% CI 0.810-0.860), respectively, whereas those for external validation were 0.748 (95% CI 0.721-0.775) and 0.814 (95% CI 0.785-0.843), respectively. Conclusions: The proposed nomogram is a reliable and robust tool for accurate prognostic prediction in patients with extremity soft tissue LMS.

Epigenetic Regulation of CXCL12 Plays a Critical Role in Mediating Tumor Progression and the Immune Response In Osteosarcoma.

The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here, we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and to impair cytotoxic T-cell homing to the tumor site. Analysis of human osteosarcoma cases further revealed that CXCL12 expression strongly correlated with overall survival. Evaluations on fresh human chemotherapy-free osteosarcoma samples also showed a positive correlation between CXCL12 concentration and the number of intratumoral lymphocytes. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth. These antitumor effects were abrogated by CXCL12-CXCR4 blockade or CD8+ T-cell depletion. Collectively, our data show that CXCL12 regulation plays a significant role in both tumor progression and immune response, and targeting CXCL12 is promising for therapeutics against osteosarcoma.Significance: Epigenetic regulation of CXCL12 controls metastasis and immune response in osteosarcoma, suggesting epigenetic therapies or therapies targeting CXCL12 have potential for therapeutic intervention in osteosarcoma. Cancer Res; 78(14); 3938-53. ©2018 AACR.

Distinct domains of the AVRPM3A2/F2 avirulence protein from wheat powdery mildew are involved in immune receptor recognition and putative effector function.

Recognition of the AVRPM3A2/F2 avirulence protein from powdery mildew by the wheat PM3A/F immune receptor induces a hypersensitive response after co-expression in Nicotiana benthamiana. The molecular determinants of this interaction and how they shape natural AvrPm3a2/f2 allelic diversity are unknown. We sequenced the AvrPm3a2/f2 gene in a worldwide collection of 272 mildew isolates. Using the natural polymorphisms of AvrPm3a2/f2 as well as sequence information from related gene family members, we tested 85 single-residue-altered AVRPM3A2/F2 variants with PM3A, PM3F and PM3FL456P/Y458H (modified for improved signaling) in Nicotiana benthamiana for effects on recognition. An intact AvrPm3a2/f2 gene was found in all analyzed isolates and the protein variant recognized by PM3A/F occurred globally at high frequencies. Single-residue alterations in AVRPM3A2/F2 mostly disrupted, but occasionally enhanced, the recognition response by PM3A, PM3F and PM3FL456P/Y458H . Residues enhancing hypersensitive responses constituted a protein domain separate from both naturally occurring polymorphisms and positively selected residues of the gene family. These results demonstrate the utility of using gene family sequence diversity to screen residues for their role in recognition. This approach identified a putative interaction surface in AVRPM3A2/F2 not polymorphic in natural alleles. We conclude that molecular mechanisms besides recognition drive AvrPm3a2/f2 diversification.

MELD-SCH: A megastudy of lexical decision in simplified Chinese.

Here we report on MELD-SCH (MEgastudy of Lexical Decision in Simplified CHinese), a dataset that contains the lexical decision data of 1,020 one-character, 10,022 two-character, 949 three-character, and 587 four-character simplified Chinese words obtained from 504 native Chinese users. It also includes a number of word-level and character-level variables. Analyses showed that the reliability of the dataset is satisfactory, as indicated by split-half correlations and comparisons with other datasets. Item-based regression showed that both word-level and character-level variables contributed significantly to the reaction times and error rates of lexical decision. Moreover, we discovered a U-shape relationship between word-length and reaction times, which has not been reported in Chinese before. MELD-SCH can facilitate research in Chinese word recognition by providing high quality normative data and information of different linguistic variables. It also encourages researchers to extend their empirical findings, which are mostly based on one-character and two-character words, to words of different lengths.

The Treatment of Fibrosis of Joint Synovium and Frozen Shoulder by Smad4 Gene Silencing in Rats.

Soft tissue fibrosis at the joint induced by inflammation is the pathological basis of frozen shoulder. In the present study, we utilized a lentiviral approach to silence the Smad4 gene in an in vitro fibrosis model of fibroblasts and an in vivo frozen shoulder model. We observed the change in the fibrosis process and the biological indicators of frozen shoulder. The in vitro fibrosis models (Rat myoblasts L6, Rat synovial cell RSC-364 and Rat chondrocytes RCs) were established using TGF-ß1 induction, and the effect of Smad4 gene silencing on fibrosis was analyzed. The method of Kanno A was employed to establish a rat model of frozen shoulder, and Smad4 in the relevant part was knocked down with the lentiviral approach. We then examined the abduction and rotation angles and the length of synovial intima and measured the inflammatory factors in effusion and the fibrotic markers of tissues. We found that Smad4 knockdown suppressed the proliferation and expression of fibrotic markers in L6, RSC-364 and RCs cells induced by TGF-ß1. MMP activity measurements showed that Smad4 knockdown significantly reversed the decrease in MMP activity in these three cell lines that were induced by TGF-ß1. Furthermore, using lentivirus in the rat frozen shoulder model, we found that Smad4 silencing attenuated the inflammatory response and fibrosis. It significantly inhibited the increase of the Vimentin, α-SMA, collagen I and III, Lama1 and Timp1 proteins in synovial tissue as well as the inflammatory factors of TNF-a, IL-1α/ß, IL-6 and IL-10 in effusion. MMP acidity assays revealed that Smad4 silencing inhibited MMP activity in the synovial, cartilage and ligament tissues in the model animals. The assessment of the phosphorylated Smad2/3 in the nuclei isolated from the synovial tissues showed that Smad4 silencing significantly inhibited the phosphorylation and subsequent nuclear translocation of Smad2/3 proteins. Moreover, Smad4-shRNA lentivirus inhibited the decrease in both the abduction and rotation angles caused by immobilization as well as the decrease in the length of the synovial intima. Based on shoulder movement data, Smad4 knockdown can increase the rotation limitation caused by immobilization. In summary, Smad4 silencing can suppress chronic inflammation and fibrosis in joint tissues by inhibiting the TGF-ß/Smad pathway and can play a positive role in the prevention and treatment of joint stiffness.

Fast and accurate finite element analysis of large-scale three-dimensional photonic devices with a robust domain decomposition method.

A fast and accurate full-wave technique based on the dual-primal finite element tearing and interconnecting method and the second-order transmission condition is presented for large-scale three-dimensional photonic device simulations. The technique decomposes a general three-dimensional electromagnetic problem into smaller subdomain problems so that parallel computing can be performed on distributed-memory computer clusters to reduce the simulation time significantly. With the electric fields computed everywhere, photonic device parameters such as transmission and reflection coefficients are extracted. Several photonic devices, with simulation volumes up to 1.9×10(4) (λ/n(avg))3 and modeled with over one hundred million unknowns, are simulated to demonstrate the application, efficiency, and capability of this technique. The simulations show good agreement with experimental results and in a special case with a simplified two-dimensional simulation.