Cement augmentation for proximal humerus fractures: a meta-analysis of randomized trials and observational studies.

INTRODUCTION: It is unclear if elderly patients treated with plate osteosynthesis for proximal humerus fractures benefit from cement augmentation. This meta-analysis aims to compare cement augmentation to no augmentation regarding healing, complications, and functional results. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized clinical trials and observational studies. Effect estimates were pooled across studies using random effects models. The primary outcome is overall complication rate. Stratified analyses were performed for types of complication (implant-related or systemic). Secondary outcomes include re-interventions, hospital stay, operation time, functional scores, and general quality of life. RESULTS: Five observational studies and one randomized controlled trial with a total of 541 patients were included. The overall complication rate was significantly lower in the augmented group (15.6% versus 25.4%, OR 0.54 (95%CI 0.33-0.87)). This was caused by a reduction of implant-related complications (10.4% vs. 19.9%, OR 0.49 (95%CI 0.28, 0.88)). No difference in humeral head necrosis was found. Data on re-intervention, hospital stay, and operation time was limited but did not show significant differences. No impact on functional scores and general quality of life was detected. CONCLUSION: This meta-analysis shows that cement augmentation may reduce overall complications, mainly by preventing implant-related complications. No difference was detected regarding need for re-intervention, functional scores, general quality of life, and hospital stay. This is the first meta-analysis on this topic. It remains to be seen whether conclusions will hold when more and better-quality data becomes available.

A natural experiment study: Low-profile double plating versus single plating techniques in midshaft clavicle fractures-Study protocol.

BACKGROUND: Single plate osteosynthesis is commonly employed when performing surgical stabilization of midshaft clavicle fractures. In recent years, a smaller structural low-profile double plating technique has been described as a possible solution for the high removal rates associated with single plating. A previous meta-analysis has demonstrated that low-profile double plating attains the same healing rates as single plating without a higher chance of fracture-related infections. This meta-analysis, however, was based on relatively small studies. Therefore, a multicentre prospective natural experiment was designed using natural variation in treatment regimens and geographical location of the trauma as treatment allocation mechanism to compare both treatments on a larger scale. This manuscript describes its protocol. MATERIAL & METHODS: Patients (≥16 years) with primary midshaft clavicle fractures that are eligible for operative treatment will be included. Treatment allocation will be determined by the geographical location of the accident and local hospital providing treatment. In two centres, single plating is the treatment of choice for these patients. In two others, low-profile double plating has become the standard treatment. For the low-profile double plating group, one superiorly positioned VariAx 2.0mm and one anterior VariAx 2.4mm or 2.7mm plate will be used. For the single plating group, the standard locally available implant will be used. A total of 336 patients will be included. The primary outcome of interest is re-intervention. Secondary outcomes include complications, operative time, length of incision, functional scores (DASH, EQ-5D-DL, VAS-Pain/Satisfaction) and cost-effectiveness. DISCUSSION: This study will determine whether low-profile double plating has significant clinical and cost-effective benefits over single plating techniques in midshaft clavicle fractures. The study will also give insight in the performance of a natural experiment study design for orthopedic trauma research. TRIAL REGISTRATION: This study has been registered on ClincialTrials.gov, identifier NCT05579873.

Intraoperative imaging in hip arthroplasty: a meta-analysis and systematic review of randomized controlled trials and observational studies.

BACKGROUND: Intraoperative fluoroscopy (IFC) is gaining popularity in total hip arthroplasty (THA), with the aim to achieve better component positioning and therefore eventually reduced revision rates. This meta-analysis investigated the benefit of IFC by comparing it to intraoperative assessment alone. The primary outcome was component positioning and the secondary outcomes included complications and revision rates. METHODS: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for both randomized clinical trials (RCT) and observational studies. Effect estimates for radiographic cup position, offset/leg length difference and outliers from a safe zone were pooled across studies using random effects models and presented as a weighted odds ratio (OR) with a corresponding 95% confidence interval (95% CI). RESULTS: A total of 10 observational studies involving 1,394 patients were included. No randomized trials were found. IFC showed no significant reduction in acetabular cup position (inclination and anteversion), offset, leg-length discrepancies, revision (none reported) or overall complication rates. CONCLUSION: The current meta-analysis found no differences in cup positioning, offset, leg length discrepancy, the incidence of complications or revision surgery. It should be acknowledged that the included studies were generally performed by experienced surgeons. The benefit of intraoperative fluoroscopy might become more evident at an early phase of the learning curve for this procedure. Therefore, its role has yet to be defined.

Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions.

Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) is widely used for mRNA quantification. To accurately measure changing gene transcript levels under different experimental conditions, the use of appropriate reference gene transcripts is instrumental. In T cell immunology, suitable reference genes have been reported for bulk CD4+ and CD8+ T cells. However, many CD4+ and CD8+ T cell subsets have been described in the past. Although they respond differently to given activation stimuli, proper validation of suitable reference genes in these subsets is lacking. In this study, we evaluated twelve commonly used reference gene products in human naïve (NV) and effector memory (EM) CD8+ T cells under non-activated and activated (2 h, 10 h and 20 h) conditions. We used five different statistical approaches for data analysis. Our results show that a number of widely used reference transcripts become differentially expressed under activating conditions. Using them as references markedly alters results as exemplified with IFNG mRNA expression. The only candidate reference gene products that remained stable during the activation process were 18S rRNA and SDHA mRNA, encouraging their usage as reference gene products for RT-qPCR experiments, when quantifying mRNA levels in human NV and EM CD8+ T cells.

Tumor-derived TGF-ß inhibits mitochondrial respiration to suppress IFN-γ production by human CD4+ T cells.

Transforming growth factor-ß (TGF-ß) is produced by tumors, and increased amounts of this cytokine in the tumor microenvironment and serum are associated with poor patient survival. TGF-ß-mediated suppression of antitumor T cell responses contributes to tumor growth and survival. However, TGF-ß also has tumor-suppressive activity; thus, dissecting cell type-specific molecular effects may inform therapeutic strategies targeting this cytokine. Here, using human peripheral and tumor-associated lymphocytes, we investigated how tumor-derived TGF-ß suppresses a key antitumor function of CD4+ T cells, interferon-γ (IFN-γ) production. Suppression required the expression and phosphorylation of Smad proteins in the TGF-ß signaling pathway, but not their nuclear translocation, and depended on oxygen availability, suggesting a metabolic basis for these effects. Smad proteins were detected in the mitochondria of CD4+ T cells, where they were phosphorylated upon treatment with TGF-ß. Phosphorylated Smad proteins were also detected in the mitochondria of isolated tumor-associated lymphocytes. TGF-ß substantially impaired the ATP-coupled respiration of CD4+ T cells and specifically inhibited mitochondrial complex V (ATP synthase) activity. Last, inhibition of ATP synthase alone was sufficient to impair IFN-γ production by CD4+ T cells. These results, which have implications for human antitumor immunity, suggest that TGF-ß targets T cell metabolism directly, thus diminishing T cell function through metabolic paralysis.