Impact of surrogate outcomes in randomized controlled trials for shoulder rotator cuff tears.

PURPOSE: Surrogate outcomes are clinical endpoints that are used as substitutes for direct measures of how a patient feels, functions, or survives. The present study aims to analyze the impact of surrogate outcomes on the results of randomized controlled trials on shoulder rotator cuff tears disorders. METHODS: Randomized controlled trials (RCTs) related to rotator cuff tear conditions published up until 2021 were retrieved from the PubMed and ACCESSSS databases. The primary outcome of the article was considered a surrogate outcome when the authors used radiological, physiologic, or functional variables. The result of the article was considered positive when results supported the intervention based on the trial's primary outcome. We recorded the sample size, the mean follow-up, and the type of funding. Statistical significance was set at p < 0.05. RESULTS: A total of 112 papers were included in the analysis. The mean sample size was 87.6 patients; mean follow-up period was 25.97 months. Thirty-six out of 112 RCTs used a surrogate outcome as a primary endpoint. More than half of papers using surrogate outcomes reported a positive finding (20 out of 36), while 10 out of 71 RCTs using patient-centered outcomes favored the intervention (14.08%, p < 0.001) [RR = 3.94 (95% CI 2.07-7.51)]. The mean sample size was smaller in trials using surrogate endpoints (75.11 vs 92.35 patients, respectively, p = 0.049), while the follow-up was shorter (14.12 m vs. 31.9 m, p < 0.001). Approximately 25% of the papers that reported surrogate endpoints (22.58%) were industry-funded projects. CONCLUSIONS: The substitution of surrogate endpoints for patient-important outcomes in shoulder rotator cuff trials quadruplicates the chances of obtaining a favorable result that favors the analyzed intervention.

NLRP3 is involved in long bone edification and the maturation of osteogenic cells.

Overexpression of the nucleotide-binding leucine-rich repeat protein 3 (NLRP3) inflammasome in chronic auto-immune diseases leads to skeletal anomalies, with severe osteopenia due to the activation of osteoclasts. Reproducing this phenotype in Nlrp3 knock-in mice has provided insights into the role of NLRP3 in bone metabolism. We studied the role of NLRP3 in physiological bone development using a complete Nlrp3 knock-out mouse model. We found impaired skeletal development in Nlrp3-/- mice, resulting in a shorter stature than that of Nlrp3+/+  mice. These growth defects were associated with altered femur bone growth, characterized by a deficient growth plate and an osteopenic profile of the trabeculae. No differences in osteoclast recruitment or activity were observed. Instead, Nlrp3-/- femurs showed a less mineralized matrix in the trabeculae than those of Nlrp3+/+  mice, as well as less bone sialoprotein (BSP) expressing hypertrophic chondrocytes. In vitro, primary osteoblasts lacking NLRP3 expression showed defective mineralization, together with the downregulation of BSP expression. Finally, follow-up by micro-CT highlighted the role of NLPR3 in bone growth, occurring early in living mice, as the osteopenic phenotype diminishes over time. Overall, our data suggest that NLRP3 is involved in bone edification via the regulation of hypertrophic chondrocyte maturation and osteoblast activity. Furthermore, the defect appeared to be transitory, as the skeleton recovered with aging.

Human placental villi contain stromal macrovesicles associated with networks of stellate cells.

Placental function is essential for fetal development and establishing the foundations for lifelong health. The placental villous stroma is a connective tissue layer that supports the fetal capillaries and villous trophoblast. All the nutrients that cross the placenta must also cross the stroma, and yet little is known about this region. This study uses high-resolution three-dimensional imaging to explore the structural complexity of this region within the placental villi. Serial block-face scanning electron microscopy and confocal microscopy were used to image the placental villous stroma in three-dimensions. Transmission electron microscopy (TEM) was used to generate high resolution two-dimensional images. Stereological approaches were used to quantify volumes of stromal constituents. Three-dimensional imaging identified stromal extracellular vesicles, which constituted 3.9% of the villous stromal volume. These stromal extracellular vesicles were ovoid in shape, had a median length of 2750 nm (range 350-7730 nm) and TEM imaging confirmed that they were bounded by a lipid bilayer. Fifty-nine per cent of extracellular vesicles were in contact with a fibroblast-like stellate cell and these vesicles were significantly larger than those where no contact was observed. These stellate cells formed local networks with adherent junctions observed at contact points. This study demonstrates that the villous stroma contains extracellular macrovesicles which are considerably larger than any previously described in tissue or plasma. The size and abundance of these macrovesicles in the villous stroma highlight the diversity of extracellular vesicle biology and their roles within connective tissues.

Socioeconomic inequalities and the equity impact of population-level interventions for adolescent health: an overview of systematic reviews.

OBJECTIVES: Despite robust evidence on health inequalities in adulthood, less attention has been paid to inequalities in adolescence. The aim of this overview was to examine systematic review (SR) evidence on the equity impact of population-level interventions intended to improve health, happiness and wellbeing for adolescents. STUDY DESIGN: An overview (review of systematic reviews). METHODS: Eleven electronic databases were systematically searched to identify SRs of population-level interventions for adolescent health. A secondary data analysis of socioeconomic inequality was conducted to identify whether SRs reported on primary studies in terms of disadvantage, by measures of socioeconomic status (SES) and by differential effects. RESULTS: 35,310 review titles were screened; 566 full texts were retrieved and 140 SRs met the predefined selection criteria. Differential intervention effects were considered in 42/140 (30%) SRs, 18/140 (13%) reported primary studies using an SES measure and 16/140 (11%) explicitly reported differential effects. 15/140 SRs (11%) explicitly focused on socioeconomic inequalities; of these 4/15 reported differential intervention effects in more detail, 7/15 concluded there was insufficient primary evidence to identify the impact of interventions on socioeconomic inequalities and 4/15 planned to examine differential effects by SES, but this was not reported further. CONCLUSIONS: Our overview identifies that there is limited SR evidence on the equity impact of population-level interventions for adolescent health. Strengthening the evidence on whether interventions narrow or widen inequalities for adolescents must be a priority for public health research.

Retaining or excising the supraspinatus tendon in complex proximal humeral fractures treated with reverse prosthesis: a biomechanical analysis in two different designs.

PURPOSE: We aimed to biomechanically evaluate the effect of the supraspinatus tendon on tuberosity stability using two different reverse shoulder arthroplasty (RSA) models for complex proximal humeral fractures (PHFs). METHODS: Four-part proximal humeral fractures were simulated in 20 cadaveric shoulders. Two different RSA designs were implemented: a glenosphere-medialized model and a glenosphere-lateralized model. Tuberosities were reconstructed, and displacement of bony fragments was measured (mm) by placing three sensors: in the humeral diaphysis (D), in the greater tuberosity (GT), and in the lesser tuberosity (LT). Axial forces were induced and measured in Newton (N). The test was performed twice in each specimen, with and without the supraspinatus tendon. The regression line (RL) was measured in mm/N. RESULTS: In the medialized model, the GT-D displacement was greater in the supraspinatus preserving model than that in the tendon excision model (p < 0.001), as well as for the LT-D displacement (p < 0.001). In the lateralized model, GT-D displacement and GT-LT distance were greater in the preserving model than that in the excision model (p < 0.001, p = 0.04). CONCLUSION: The supraspinatus tendon resection leads to a more biomechanically stable tuberosity construct when performing RSA for PHFs, while the rest of the rotator cuff tendons (infraspinatus and teres minor) are retained in the greater tuberosity. LEVEL OF EVIDENCE: Basic science study. Cadaveric study.

Phase contrast synchrotron radiation computed tomography of muscle spindles in the mouse soleus muscle.

Muscle spindles are skeletal muscle sensory organs involved in the sensation of position and movement of the body. We have explored the capability of phase contrast computed tomography to visualise muscle spindles in murine skeletal muscle. In particular, we have validated the visualisation of nerve fibres through phase contrast computed tomography using light microscopy on stained histological sections. We further present the first three-dimensional visualisation of muscle spindles in mouse soleus skeletal muscle in conjunction with the neurovascular bundle associated with it.

Surgical treatment of proximal humeral fractures with the transosseous suture fixation.

BACKGROUND: The surgical treatment of displaced proximal humeral fractures is commonly affected by implant-related complications. We evaluated the functional and radiographic results of transosseous suture fixation in a series of displaced proximal humeral fractures (PHF). METHODS: Sixty-four patients were retrospectively classified by age, sex, and the Neer fracture classification. Two-part greater tuberosity (2pGT) displaced fractures and 3-part (varus and valgus) and 4-part valgus impacted fractures were managed with fragment reduction and transosseous suture fixation. Patients with minimum follow-up of 24 months and assessed with the Constant-Murley score (CMS) were included. Radiological and medical complications, as well as reinterventions were also recorded. RESULTS: Forty-six patients with a mean follow-up of 58 (24-132) and a mean age of 58 years old were analyzed. Patients with 2pGT (n = 10) fractures had a CMS of 76 points (59-89); patients with 3-part fractures (n = 22) had a score of 67 points (13-91); and those with 4-part fractures (n = 14) had a score of 64 (24-76) points. The overall complication rate was 6 out of 46, and 4 patients required reintervention for different reasons. Patients presenting with 3-part varus fractures had significantly lower functional outcomes scores (p = 0.007). Humeral head osteonecrosis was present in 9 patients and significantly affected the functional outcomes (p < 0.05). However, only three out of nine patients with osteonecrosis required subsequent surgery at the indicated follow-up. CONCLUSIONS: The fracture reduction and transosseous fixation technique represents a safe technique with low complication and reintervention rates. The presence of humeral head necrosis did not lead to subsequent surgical intervention because no hardware had protruded. LEVEL OF EVIDENCE: Level IV, retrospective study.

Reverse shoulder arthroplasty for acute proximal humeral fractures: Postoperative complications at 7 days, 90 days and 1 year.

BACKGROUND: In the last decade, the biomechanics of reverse shoulder arthroplasty (RSA) for proximal humeral fractures in the elderly have led to more functional outcomes and greater pain relief. However, its use has also introduced a significant rate of complications. The purpose of this study is to assess the complication rate of RSA in these cases as well as the relationship to ASA score and basic disease history. METHODS: We evaluate patients who underwent RSA due to acute proximal humeral fractures at three hospitals from 2010 to 2016. We analyze previous disease and anticoagulant treatment, American Society of Anesthesiologists (ASA) Physical Status Classification, and the transfusion rate to correlate these factors with major and minor postoperative complications at 7, 90, and 365 days. RESULTS: We include 103 patients (104 shoulders) over 65 years of age. Mean age is 77.31 years (62-91), 20 of which are male. The overall rate of complications is 25%, with 17.4% minor and 7.6% major complications. We observe a statistically significant relationship between a higher ASA score (3,4) and major complication at 90 days (p = 0.024) and a trend (p = 0.072) towards a higher ASA score with minor complication during the first week. Rheumatoid disease significantly increases major complications at 90 days (p = 0.037). The transfusion rate is 11.5%. CONCLUSIONS: The overall major complication rate of RSA for acute fractures is low in the elderly population. Although, the patient's history (e.g. previous rheumatoid pathology, neurological diseases, or anticoagulant treatment) as well as their ASA score should be considered before RSA surgery. The higher the ASA score and the presence of rheumatoid disease, leads to a higher rate of major complications during the first 90 days after surgery. LEVEL OF EVIDENCE: Level IV; Case series; Treatment study.

Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions.

Bicuspid aortic valve (BAV) disease remains the most common congenital cardiac disease and is associated with an increased risk of potentially fatal aortopathy including aortic aneurysm and dissection. Mutations in the NOTCH1 gene are one of only a few genetic anomalies identified in BAV disease; however evidence for defective NOTCH signaling, and its involvement in the characteristic histological changes of VSMC apoptosis and differentiation in ascending aortae of BAV patients is lacking. This review scrutinizes the evidence for the interactions of NOTCH signaling, cellular differentiation and apoptosis in the context of aortic VSMCs and provides focus for future research efforts in the diagnosis of BAV aortopathy and prevention of catastrophic complications through NOTCH signaling manipulation.

Do we publish what we preach? Analysis of Spanish Shoulder and Elbow Surgery Society publication rates. / ¿Publicamos lo que predicamos? Tasa de publicación de los congresos de la Sociedad Española de Cirugía de Hombro y Codo.

INTRODUCTION: The purpose of this study is to analyse the publication rate of studies presented as podium presentations in the Spanish Society of Shoulder and Elbow Surgery (SECHC) congresses. METHODS: One hundred and twenty-two abstracts presented at the SECHC congresses held in 2007, 2009 and 2011 were included for the purpose of the study. The oral communications were categorized by study type, sample included and follow-up. In June 2017, possible publications of these studies were searched in PubMed. Type of study, delay in publication, journal and impact factor obtained were recorded. The concordance between the information presented at the congress and their subsequent full-text publications was analysed. RESULTS: The publication rate was 17.21% (21 of the 122 abstracts studied) after 6 years, with a mean time spent for publications of 36.71 months, and a mean impact factor of 1.51. There were no differences between results initially presented at the congresses and those subsequently published (P>0.05). DISCUSSION: The majority of papers presented at SECHC congresses do not end up with a publication. The papers that are published do not usually contain significant differences compared to the content delivered at the congress.