Proximal femoral varus osteotomy for Legg-Calvé-Perthes disease: Do age and lateral pillar classifications influence short-to-mid-term clinical and radiological outcomes?

INTRODUCTION: Proximal femoral varus osteotomy (FVO) is one of the most used treatment methods with acceptable outcomes for Legg-Calvé-Perthes disease (LCPD). We aimed to investigate the influence of age at disease onset and the Lateral Pillar classification on clinical and radiological outcomes of FVO surgery LCPD patients between 6-12years of age. HYPOTHESIS: Proximal FVO surgery in the early fragmentation phase of LCPD patients led to acceptable clinical and radiographic outcomes in a 3-year follow-up, regardless of preoperative age and Herring type. MATERIAL AND METHODS: Fifty patients with LCPD (Herring groups B, B/C, and C) who underwent FVO were retrospectively reviewed. We evaluated radiological [center-edge angle, extrusion index, epiphyseal index, acetabular index, articulo-trochanteric distance (ATD)] and clinical [hip abduction range of motion (ROM), Trendelenburg sign, pain, and Harris hip score (HHS)] outcomes with a follow-up of 37.3±10.5months (range: 24-180months). Finally, the overall treatment outcome was assessed using the Stulberg classification. RESULTS: The ROC curve analysis did not reveal any significant relationship between age and clinical or radiological outcomes, and there was no predictable age cut-off for surgical outcomes (p=0.13). No significant difference was found in Stulberg classification at the follow-up between patients with type B, B/C, and C of the lateral pillar (p>0.05). DISCUSSION: Our results demonstrated that open-wedge proximal FVO surgery in the early fragmentation phase of LCPD patients led to acceptable clinical and radiographic outcomes in a 3-year follow-up. Each sample of our study was very small and a lot of variables were measured, making this result not adequately strong enough to draw a robust conclusion. However, FVO surgery remains a possible suggestion for patients in the early fragmentation phase, and age and lateral pillar type may not be limiting factors. LEVEL OF EVIDENCE: IV; therapeutic retrospective cohort.

Unlocking c-MET: A comprehensive journey into targeted therapies for breast cancer.

Breast cancer is the most common malignancy among women, posing a formidable health challenge worldwide. In this complex landscape, the c-MET (cellular-mesenchymal epithelial transition factor) receptor tyrosine kinase (RTK), also recognized as the hepatocyte growth factor (HGF) receptor (HGFR), emerges as a prominent protagonist, displaying overexpression in nearly 50% of breast cancer cases. Activation of c-MET by its ligand, HGF, secreted by neighboring mesenchymal cells, contributes to a cascade of tumorigenic processes, including cell proliferation, metastasis, angiogenesis, and immunosuppression. While c-MET inhibitors such as crizotinib, capmatinib, tepotinib and cabozantinib have garnered FDA approval for non-small cell lung cancer (NSCLC), their potential within breast cancer therapy is still undetermined. This comprehensive review embarks on a journey through structural biology, multifaceted functions, and intricate signaling pathways orchestrated by c-MET across cancer types. Furthermore, we highlight the pivotal role of c-MET-targeted therapies in breast cancer, offering a clinical perspective on this promising avenue of intervention. In this pursuit, we strive to unravel the potential of c-MET as a beacon of hope in the fight against breast cancer, unveiling new horizons for therapeutic innovation.

Does Using Highly Porous Tantalum in Revision Total Hip Arthroplasty Reduce the Rate of Periprosthetic Joint Infection? A Systematic Review and Meta-Analysis.

Background: Studies suggest tantalum (Ta) implants may have inherent antibacterial properties. However, there is no consensus regarding the effectiveness of Ta in preventing periprosthetic joint infection (PJI) after revision total hip arthroplasty (rTHA). Methods: We searched 5 main databases for articles reporting the rate of PJI following rTHA using Ta implants from inception to February 2022. The PJI rates of the Ta group were meta-analyzed, compared with the control group, and represented as relative risks (RRs) in forest plots. Results: We identified 67 eligible studies (28,414 joints) for assessing the prevalence of PJI following rTHA using Ta implants. Among these studies, only 9 compared the Ta implant group with a control group. The overall PJI rate following rTHA using Ta implants was 2.9% (95% confidence interval [CI]: 2.2%-3.8%), while it was 5.7% (95% CI = 4.1%-7.8%) if only septic revisions were considered. Comparing the Ta and control groups showed a significantly lower PJI rate following all-cause rTHA with an RR = 0.80 (95% CI = 0.65-0.98, P < .05). There was a trend toward lower reinfection rates in the Ta group after rTHA in septic cases, although the difference was not statistically significant (RR = 0.75, 95% CI = 0.44-1.29, P = .30). Conclusions: Ta implants are associated with a lower PJI rate following all-cause rTHA but not after septic causes. Despite positive results, the clinical significance of Ta still remains unclear since the PJI rate was only reduced by 20%. Level of Evidence: IV.

The effects of low-fat dairy products fortified with 1500 IU vitamin D3 on serum liver function biomarkers in adults with abdominal obesity: a randomized controlled trial.

INTRODUCTION: Vitamin D deficiency has been reported to affect liver function biomarkers. This study was aimed to investigate the effect of consuming vitamin D fortified low-fat dairy products on liver function tests in adults with abdominal obesity. METHODS: This total blinded randomized controlled trial was undertaken on otherwise healthy abdominally obese adults living in Mashhad, Iran. Milk and yogurt were fortified with 1500 IU vitamin D3 nano-capsules. Participants were randomized to receive fortified milk (n = 73), plain milk (n = 73), fortified yogurt (n = 69), and plain yogurt (n = 74) for 10 weeks. Blood samples were taken at baseline and at the end of the study to assess serum levels of vitamin D, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), and Gamma glutamyl transferase. RESULTS: A total of 289 participants completed the study (54% female). The groups were homogenous in terms of age, sex, weight, energy intake, and physical activity level (p-value > 0.05). After the trial, vitamin D serum levels were significantly increased in both groups receiving fortified products (both p < 0.001). There was a significant time*group effect only in serum ALP (p < 0.001). CONCLUSION: Consumption of dairy products fortified by 1500 IU vitamin D3 might have detrimental effects on serum levels of some liver enzymes in individuals with abdominal obesity. Further studies needed to determine these effects and underlying mechanisms. TRIAL REGISTRATION: IRCT20101130005280N27 .

miRNA expression in COVID-19.

Coronavirus disease 2019 (COVID-19) is regarded as a challenge in health system. Several studies have assessed the immune-related aspect of this disorder to identify the host-related factors that affect the course of COVID-19. microRNAs (miRNAs) as potent regulators of immune responses have gained much attention in this regard. Recent studies have shown aberrant expression of miRNAs in COVID-19 in association with disease course. Differentially expressed miRNAs have been enriched in pathways related with inflammation and antiviral immune response. miRNAs have also been regarded as potential therapeutic targets in COVID-19, particularly for management of pathological consequences of COVID-19. In the current review, we summarize the data about dysregulation of miRNAs in COVID-19.

Comparative Study of Vascular Endothelial Growth Factor in Exudative and Transudative Pleural Effusion.

Background: Increased vascular permeability is one of the main mechanisms in the production of pleural effusion (PE) and vascular endothelial growth factor (VEGF) has a significant role in its pathogenesis. This study aimed to compare pleural levels of VEGF in transudative and exudative PEs besides the other pleural markers. Materials and Methods: In this prospective cross-sectional study, 80 patients with PE were divided into 4 groups as transudative (N=15), parapneumonic (N=15), tuberculosis (N=25), and malignant (N=25) PE. Biochemical tests measured the pleural protein, LDH, cholesterol, glucose, polymorphonuclear cell (PMN), and lymphocyte. ELISA measured the pleural VEGF level. Results: Out of 80 patients, 51 were male, and the total mean age was 55.34±18.53. There were significant differences in pleural VEGF between exudative and transudative effusion (P<0.001) and between malignant and benign effusion (P=0.014). The highest mean difference in pleural VEGF levels was seen in the comparison of transudative and malignant groups (Mean difference=-136.56; P<0.002). The VEGF level in 3 groups was not significantly different; transudative vs tuberculous, parapneumonic vs tuberculous, and parapneumonic vs malignant. Furthermore, VEGF higher than 73.09 pg/ml had a 64% sensitivity and 82% specificity for the diagnosis of malignancy. Among pleural markers (VEGF, protein, LDH, and glucose), VEGF had the highest area under curve (AUC=0.734). Moreover, pleural protein, LDH, and glucose levels significantly correlated with pleural VEGF; however, pleural cholesterol, PMN, and lymphocyte were not correlated. Conclusion: VEGF is assumed as an important factor in the pathogenesis of exudative PE, especially malignant effusion. It can distinguish between lymphocytic exudative PEs.

A bioengineering method for modeling alveolar Rhabdomyosarcoma and assessing chemotherapy responses.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignant tumor. Treatment of RMS usually includes primary tumor resection along with systemic chemotherapy. Two-dimensional (2D) cell culture systems and animal models have been extensively used for investigating the potential efficacy of new RMS treatments. However, RMS cells behave differently in 2D culture than in vivo, which has recently inspired the adoption of three-dimensional (3D) culture environments. In the current paper, we will describe the detailed methodology we have developed for fabricating a 3D engineered model to study alveolar RMS (ARMS) in vitro. This model consists of a thermally cross-linked collagen disk laden with RMS cells that mimics the structural and bio-chemical aspects of the tumor extracellular matrix (ECM). This process is highly reproducible and produces a 3D engineered model that can be used to analyze the cytotoxicity and autophagy induction of drugs on ARMS cells. The most improtant bullet points are as following:•We fabricated 3D model of ARMS.•The current ARMS 3D model can be used for screening of chemotherapy drugs.•We developed methods to detect apoptosis and autophagy in ARMS 3D model to detect the mechansims of chemotherapy agents.