Closed Reduction Techniques Are Associated With Fewer Complications Than Open Reductions in Treating Moderately Displaced Pediatric Lateral Humeral Condyle Fractures: A Multicenter Study.

INTRODUCTION: Lateral humeral condyle (LC) fractures are the second most common pediatric elbow fractures. Traditionally, displaced fractures have been treated with open reduction although recent studies have demonstrated successful outcomes of closed reduction for similar injuries. This study investigates the outcomes comparing open and closed reduction in a large cohort of children with moderately displaced (Song classification types 1 to 4) lateral humeral condyle fractures. METHODS: Retrospective data from patients aged between 1 and 12 years treated for lateral condyle fractures was collected from 6 academic level 1 trauma centers between 2005 and 2019. Data was collected on patient demographics, radiographic parameters, reduction type, type of hardware fixation, and fracture patterns. Complications recorded include infections, reoperations for nonunion, osteonecrosis, and elbow stiffness. RESULTS: An initial 762 fractures were identified. After excluding Song 5 cases, a total of 480 fractures met inclusion criteria, with 202 (42%) treated with closed reduction and 278 (58%) treated with open reduction. Demographics and injury characteristics were similar across the 2 reduction cohorts. After propensity score matching, delayed healing (52% vs. 28%; OR: 2.88, 95% CI: 1.97-4.22; P<0.0001) and stiffness (22% vs. 10%; OR 2.42, 95% CI: 1.42-4.13; P=0.0012) were significantly higher in the open reduction group. No differences in the rates of infection or nonunion (3% CR and 1% OR) were noted between the 2 groups. CONCLUSION: This study demonstrates that moderately displaced lateral condyle fractures requiring open reduction are more likely to have elbow stiffness and delayed healing when compared with the ones treated with closed reduction. For these reasons, we propose attempting closed reduction techniques as the first line of treatment in moderately displaced lateral humeral condyle fractures (if anatomic articular reduction can be achieved) to attain better patient outcomes.

Prior Bariatric Surgery is Associated with Improved Total Hip Arthroplasty Outcomes in Patients Who Have Obesity: A National Cohort Study with 6 Years of Follow-Up.

BACKGROUND: Obesity is a risk factor for end-stage hip osteoarthritis (OA). While total hip arthroplasty (THA) is commonly performed to reduce pain and improve function associated with OA, obesity has been associated with an increased risk of complications after THA. Although bariatric surgery may also be utilized to reduce weight, the impact of bariatric surgery on THA outcomes remains inadequately understood. METHODS: This retrospective cohort analysis utilized multicenter electronic medical record data ranging from 2003 to 2023. Patients who have obesity who underwent THA were stratified based on prior bariatric surgery. The final bariatric cohort comprised 451 patients after propensity score matching. Complication rates and revision risks were compared between cohorts at six, 24, and 72 months. Additional analysis stratified patients by interval between bariatric surgery and THA. RESULTS: At six-month follow-up, the bariatric cohort had significantly lower risks of surgical site infection (SSI), wound dehiscence, and deep vein thrombosis (DVT). At 24 months, the bariatric cohort had a lower risk of DVT. At 72 month follow-up, the bariatric cohort had reduced rates of revision, mortality, cardiac morbidity, and Clavien-Dindo grade IV complications. CONCLUSION: Obese patients who underwent bariatric surgery prior to THA experienced reduced medical complications at all time points and reduced rates of revision at 72 months relative to a matched cohort who did not undergo bariatric surgery.

Duration of Postvaccination Neutralizing Antibodies to SARS-CoV-2 and Medication Effects: Results from the Safety and Immunogenicity of COVID-19 Vaccination in Systemic Immune-Mediated Inflammatory Diseases Cohort Study.

OBJECTIVE: In the face of the ongoing circulation of SARS-CoV-2, the durability of neutralization post-COVID-19 vaccination in immune-mediated inflammatory disease (IMID) is a key issue, as are the effects of medications. METHODS: Adults (n = 112) with inflammatory bowel disease, psoriasis/psoriatic arthritis, rheumatoid arthritis, spondylarthritis, and systemic lupus were recruited from participating Canadian medical centers from 2021 to 2023. We focused on log-transformed neutralization (lentivirus methods) as a continuous outcome, with separate models for wild-type and Omicron strains BA.1 and BA.5. RESULTS: Compared with 30 to 120 days postvaccination, subsequent periods were associated with greater neutralization in unadjusted models for wild-type, BA.1, and BA.5 strains and against the BA.1 strain in adjusted models. Rituximab was associated with lower neutralization for the BA.1 strain in adjusted models, with a similar trend for BA.5. In methotrexate users, there were trends for less neutralization of BA.1 and BA.5 in all unadjusted models, whereas in adjusted models, there was significantly lower neutralization only for the wild type. Three or more doses and Omicron-specific vaccines were both independently associated with better neutralization ability for all three strains. A COVID-19 infection within six months before sampling was associated with higher neutralization of wild type and BA.1 in adjusted analyses. Anti-tumor necrosis factor agents were associated with lower neutralization ability for BA.5 in adjusted analyses. CONCLUSION: Neutralization responses in immunosuppressed individuals with IMID were durable over time and were augmented by more than three doses and Omicron-specific vaccines. Less neutralization was seen with certain medications. Our work clarifies the joint effects of vaccine history, infection, and medications on COVID-19 immunity.

Characterization of Organic Anion and Cation Transport in Three Human Renal Proximal Tubular Epithelial Models.

The polarised expression of specific transporters in proximal tubular epithelial cells is important for the renal clearance of many endogenous and exogenous compounds. Thus, ideally, the in vitro tools utilised for predictions would have a similar expression of apical and basolateral xenobiotic transporters as in vivo. Here, we assessed the functionality of organic cation and anion transporters in proximal tubular-like cells (PTL) differentiated from human induced pluripotent stem cells (iPSC), primary human proximal tubular epithelial cells (PTEC), and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1). Organic cation and anion transport were studied using the fluorescent substrates 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP) and 6-carboxyfluorescein (6-CF), respectively. The level and rate of intracellular ASP accumulation in PTL following basolateral application were slightly lower but within a 3-fold range compared to primary PTEC and RPTEC/TERT1 cells. The basolateral uptake of ASP and its subsequent apical efflux could be inhibited by basolateral exposure to quinidine in all models. Of the three models, only PTL showed a modest preferential basolateral-to-apical 6-CF transfer. These results show that organic cation transport could be demonstrated in all three models, but more research is needed to improve and optimise organic anion transporter expression and functionality.

Epidemiology of Pediatric Firearm Injuries in the United States: The Progression of Gunshot Injury Rates Through the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: Ballistic injuries among pediatric populations have become a public health crisis in the United States. The surge in firearm injuries among children has outpaced other causes of death. This study aims to assess the trend in pediatric gunshot injuries (GSIs) over the last decade and investigate the impact, if any, of the pandemic on GSIs statistics. METHODS: A comprehensive retrospective analysis was conducted using a federated, real-time national database. A total of 15,267,921 children without GSIs and 6261 children with GSIs between 2017 and 2023 were identified. The study evaluated the incidence and annual proportions of GSIs among different demographics. In addition, the incidence proportions per 100,000 for accidental, nonaccidental, fracture-related, and fatal GSIs were analyzed. RESULTS: The incidence proportions per 100,000 for GSIs, accidental GSIs, nonaccidental GSIs, fatal GSIs, wheelchair-bound cases, and fracture-related GSIs increased significantly from 2017 to 2023, going from 9.7 to 22.8 (Relative Risk: 2.342, 95% CI: 2.041, 2.687, P < 0.001). The overall increase was mostly a result of accidental GSI when compared with nonaccidental (incidence proportion 25.8 vs 2.1; P < 0.001) in 2021 at the height of the pandemic. In patients with an accidental GSI, the incidence proportion per 100k between 2017 and 2023 increased from 8.81 to 21.11 (Relative Risk: 2.397, 95% CI: 2.076, 2.768, P < 0.001). CONCLUSION: The study supports the shift in the leading cause of death among children from motor vehicle accidents to GSIs, with the continued rise in rates despite the coronavirus disease 2019 pandemic. Accidental injuries constituted the majority of GSIs, indicating the need for enhanced gun safety measures, including requirements for gun storage, keeping firearms locked and unloaded, requiring child supervision in homes with guns, and enforcing stricter punishments as penalties. Comprehensive efforts are required to address this public health crisis. Pediatricians play a vital role in counseling and educating families on firearm safety. LEVEL OF EVIDENCE: Level III.

Reply to Tabeling et al. Comment on "Grabala et al. Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study. J. Clin. Med. 2024, 13, 1529".

We are immensely gratified by the considerable interest our study has garnered [...].

When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Valorization of Crab Shells as Potential Sorbent Materials for CO2 Capture.

This study delves into the potential advantage of utilizing crab shells as sustainable solid adsorbents for CO2 capture, offering an environmentally friendly alternative to conventional porous adsorbents, such as zeolites, silicas, metal-organic frameworks (MOFs), and porous carbons. The investigation focuses on crab shell waste, which exhibits inherent natural porosity and N-bearing groups, making them promising candidates for CO2 physisorption and chemisorption applications. Selective deproteinization and demineralization treatments were used to enhance textural properties while preserving the natural porous structure of the crab shells. The impact of deproteinization and demineralization treatments on CO2 adsorption and speciation at the atomic scale, via solid-state NMR, and correlated findings with textural properties and biomass composition were investigated. The best-performing sample exhibits a surface area of 36 m2/g and a CO2 adsorption capacity of 0.31 mmol/g at 1 bar and 298 K, representing gains of ∼3.5 and 2, respectively, compared to the pristine crab shell. These results underline the potential of fishing industry wastes as a cost-effective, renewable, and eco-friendly source to produce functional porous adsorbents.

Lumbopelvic fixation in the treatment of spinopelvic dissociation: union, complications, and neurologic outcomes of a multicenter case series.

PURPOSE: To review outcomes of spinopelvic dissociation treated with open lumbopelvic fixation. METHODS: We reviewed all cases of spinopelvic dissociation treated at three Level-I trauma centers with open lumbopelvic fixation, including those with adjunctive percutaneous fixation. We collected demographic data, associated injuries, pre- and postoperative neurologic status, pre- and postoperative kyphosis, and Roy-Camille classification. Outcomes included presence of union, reoperation rates, and complications involving hardware or wound. RESULTS: From an initial cohort of 260 patients with spinopelvic dissociation, forty patients fulfilled inclusion criteria with a median follow-up of 351 days. Ten patients (25%) had a combination of percutaneous iliosacral and open lumbopelvic repair. Average pre- and postoperative kyphosis was 30 degrees and 26 degrees, respectively. Twenty patients (50%) had neurologic deficit preoperatively, and eight (20%) were unknown or unable to be assessed. All patients presenting with bowel or bladder dysfunction (n = 12) underwent laminectomy at time of surgery, with 3 patients (25%) having continued dysfunction at final follow-up. Surgical site infection occurred in four cases (10%) and wound complications in two (5%). All cases (100%) went on to union and five patients (13%) required hardware removal. CONCLUSION: Open lumbopelvic fixation resulted in a high union rate in the treatment of spinopelvic dissociation. Approximately 1 in 6 patients had a wound complication, the majority of which were surgical site infections. Bowel and bladder dysfunction at presentation were common with the majority of cases resolving by final follow-up when spinopelvic dissociation had been treated with decompression and stable fixation.

Development of a membrane-disruption assay using phospholipid vesicles as a proxy for the detection of cellular membrane degradation.

Snakebite envenoming is a global health issue that affects millions of people worldwide, and that causes morbidity rates surpassing 450,000 individuals annually. Patients suffering from snakebite morbidities may experience permanent disabilities such as pain, blindness and amputations. The (local) tissue damage that causes these life-long morbidities is the result of cell- and tissue-damaging toxins present in the venoms. These compounds belong to a variety of toxin classes and may affect cells in various ways, for example, by affecting the cell membrane. In this study, we have developed a high-throughput in vitro assay that can be used to study membrane disruption caused by snake venoms using phospholipid vesicles from egg yolk as a substrate. Resuspended chicken egg yolk was used to form these vesicles, which were fluorescently stained to allow monitoring of the degradation of egg yolk vesicles on a plate reader. The assay proved to be suitable for studying phospholipid vesicle degradation of crude venoms and was also tested for its applicability for neutralisation studies of varespladib, which is a PLA2 inhibitor. We additionally made an effort to identify the responsible toxins using liquid chromatography, followed by post-column bioassaying and protein identification using high-throughput venomics. We successfully identified various toxins in the venoms of C. rhodostoma and N. mossambica, which are likely to be involved in the observed vesicle-degrading effect. This indicates that the assay can be used for screening the membrane degrading activity of both crude and fractionated venoms as well as for neutralisation studies.

Disparities Exist in the Experience of Financial Burden Among Orthopedic Trauma Patients: A Systematic Review.

PURPOSE OF REVIEW: There are substantial costs associated with orthopedic injury and management. These costs are likely not experienced equally among patients. At the level of the healthcare and hospital systems, disparities in financial burden and patient demographics have already been identified among orthopedic trauma patients. Accordingly, disparities may also arise at the level of the patient and how they experience the cost of their care. We sought to determine (1) how patient demographics are associated with financial burden/toxicity and (2) if patients experience disproportionate financial burden/toxicity and social support secondary to their economic standing. RECENT FINDINGS: It has been described that there is an inequitable experience in clinical and economic outcomes in certain socioeconomic demographics leading to disparities in financial burden. It has been further reported that orthopedic injury, management, and outcomes are not experienced equitably among all demographic and socioeconomic groups. Ten articles met inclusion criteria, among which financial burden was disproportionately experienced amid orthopedic trauma patients across age, gender, race, education, and marital status. Financial hardship was also unequally distributed among different levels of income, employment, insurance status, and social deprivation. Younger, female, non-White, and unmarried patients experience increased financial burden. Patients with less education, lower income, limited or no insurance, and greater social deprivation disproportionately experienced financial toxicity compared to patients of improved economic standing. Further investigation into policy changes, social support, and barriers to appropriate care should be addressed to prevent unnecessary financial burden and promote greater patient welfare.

Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study.

Background: The management of spinal deformities diagnosed before the age of 10 is critical due to the child's development, skeletal system, and growth mechanism. Magnetically controlled growing rods (MCGRs) are a surgical treatment option for the growing spine. The aim of this study was to analyze the radiological findings of patients treated with MCGRs for early-onset scoliosis (EOS) of various etiologies. We hypothesized that the MCGRs could provide acceptable long-term radiographic results, such as an increase in the T1-T12 and T1-S1 height and significant overall deformity correction. Methods: We retrospectively reviewed 161 EOS patients with a combined total of 302 MCGRs inserted at five institutions between 2016 and 2022 with a mean follow-up of at least two years. The Cobb angle of the major curve (MC), thoracic kyphosis (TK), lumbar lordosis (LL), and T1-T12 and T1-S1 height measurements were assessed before, after, and during the follow-up. Results: Among the 90 female and 71 male patients, there were 51 neurological, 42 syndromic, 58 idiopathic, and ten congenital scoliosis etiologies. Of the patients, 73 were aged under six years old. The mean follow-up time was 32.8 months. The mean age at placement of the MCGRs was 7 years and that at the last follow-up after fusion surgery was 14.5 years. The mean MC before the initial surgery was 86.2°; following rod implantation, it was 46.9°, and at the last follow-up visit, it was 45.8°. The mean correction rate among the etiology subgroups was from 43% to 50% at follow-up. The mean TK was noted as 47.2° before MCGR implantation, 47.1° after MCGR placement, and 44.5° at the last follow-up visit. The mean T1-T12 height increased by 5.95 mm per year, with a mean T1-S1 height of 10.1 mm per year. Conclusions: MCGR treatment allowed for an average correction of the curvature by 50% during the period of lengthening, while controlling any deformity and growth of the spine, with a significant increase in the T1-T12 and T1-S1 values during the observation period. MCGR treatment in EOS carries a risk of complications. While congenital and syndromic EOS often have short and less flexible curves in those groups of patients, single rods can be as effective and safe. Definitive fusion results in the mean final coronal correction between the start of MCGR treatment and after undergoing PSF of approximately 70%. The mean T1-T12 spinal height increased by 75 mm, while the T1-S1 spinal height gained a mean of 97 mm.

Residual Disease Activity in Canadian Patients With Psoriatic Arthritis Treated With Advanced Therapies: Results From a Multiregistry Analysis (UNISON-PsA).

OBJECTIVE: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA. METHODS: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies. RESULTS: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East. CONCLUSION: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment.

The decline of kilkas, sturgeons and seals in the Caspian Sea: The potential of qualitative loop analysis for the cumulative assessment of multiple drivers of stress.

Multiple stressors often act concomitantly on ecosystems but detection of species responses follows the "single species-single driver" strategy, and cumulative impacts are seldom considered. During 1990-2010, multiple perturbations in the Caspian Sea, led to the decline of kilka, sturgeon and Caspian seal populations. Specific causes for their collapse were identified but a cumulative assessment has never been carried out. Using loop analysis, a qualitative modelling technique suitable in poor-data contexts, we show how multiple drivers can be combined to assess their cumulative impact. We confirm that the decline of kilka, sturgeon and Caspian seal populations is compatible with a net effect of the concomitant perturbations. Kilkas collapse was certainly due to the outburst of M. leidyi and overfishing. In addition, the excess nutrient might have conspired to reduce these populations. The interplay between concurrent drivers produces trade-offs between opposite effects and ecosystem management must face this challenge.

The shifting trends in the epidemiology and risk factors of non-accidental fractures in children.

BACKGROUND: Fractures are a common presentation of non-accidental trauma (NAT) in the pediatric population. However, the presentation could be subtle, and a high degree of suspicion is needed not to miss NAT. OBJECTIVE: To analyze a comprehensive database, providing insights into the epidemiology of fractures associated with NAT. PARTICIPANTS AND SETTING: The TriNetX Research Network was utilized for this study, containing medical records from 55 healthcare organizations. TriNetX was queried for all visits in children under the age of 6 years from 2015 to 2022, resulting in a cohort of over 32 million. METHODS: All accidental and non-accidental fractures were extracted and analyzed to determine the incidence, fracture location, and demographics of NAT. Statistical analysis was done on a combination of Python and Epipy. RESULTS: Overall, 0.36 % of all pediatric patients had a diagnosis of NAT, and 4.93 % of fractures (34,038 out of 689,740 total fractures) were determined to be non-accidental. Skull and face fractures constituted 17.9 % of all NAT fractures, but rib/sternum fractures had an RR = 6.7 for NAT. Children with intellectual and developmental disability (IDD) or autism spectrum disorder (ASD) had a 9 times higher risk for non-accidental fractures. The number of non-accidental fractures significantly increased after 2019. CONCLUSIONS: The study findings suggest that nearly 1 out of all 20 fractures in children under age 6 are caused by NAT, and that rib/sternum fractures are most predictive of an inflicted nature. The study also showed a significant increase in the incidence of NAT, during and after the pandemic.

Evidence from personal ornaments suggest nine distinct cultural groups between 34,000 and 24,000 years ago in Europe.

Mechanisms governing the relationship between genetic and cultural evolution are the subject of debate, data analysis and modelling efforts. Here we present a new georeferenced dataset of personal ornaments worn by European hunter-gatherers during the so-called Gravettian technocomplex (34,000-24,000 years ago), analyse it with multivariate and geospatial statistics, model the impact of distance on cultural diversity and contrast the outcome of our analyses with up-to-date palaeogenetic data. We demonstrate that Gravettian ornament variability cannot be explained solely by isolation-by-distance. Analysis of Gravettian ornaments identified nine geographically discrete cultural entities across Europe. While broadly in agreement with palaeogenetic data, our results highlight a more complex pattern, with cultural entities located in areas not yet sampled by palaeogenetics and distinctive entities in regions inhabited by populations of similar genetic ancestry. Integrating personal ornament and biological data from other Palaeolithic cultures will elucidate the complex narrative of population dynamics of Upper Palaeolithic Europe.

Risk Factors for Stiffness After Surgical Treatment of Pediatric Humeral Lateral Condyle Fractures: Results of a Multicenter Study.

INTRODUCTION: Pediatric humeral lateral condyle fractures are the second most common elbow fractures. Their treatment presents challenges due to physeal and intra-articular involvement. Postoperative stiffness is a common concern that can limit limb functionality. This study aims to identify risk factors for postoperative stiffness in a large cohort of these fractures across multiple institutions. METHODS: A large, multicenter retrospective review of medical records from 6 level I trauma centers was conducted. Data from children aged 1 to 12 years with lateral condyle fractures treated between 2005 and 2019 were collected. Elbow stiffness was defined in the present study as having a limited elbow ROM that led to requiring a physical or occupational therapy referral or needing surgical treatment to address stiffness. Relevant patient demographics, fracture characteristics, treatment approaches, and complications were analyzed. RESULTS: Six hundred sixty-five fractures were analyzed. The average patient age was 8.8 years with 21% experiencing stiffness. The stiffness group had older patients, a higher incidence of elbow dislocations, a higher rate of open reduction, and more severe fracture patterns. Multivariate regression analysis identified open reduction, increased age, and concurrent elbow dislocation as significant risk factors for stiffness. Patients with stiffness commonly utilized only physical or occupational therapy (96%), while a small percentage (4%) required surgical interventions. CONCLUSIONS: This study highlights the risk factors for postoperative stiffness in pediatric humeral lateral condyle fractures, namely increased age, concomitant elbow dislocation, and treatment with open reduction. Families of older patients or severe fracture patterns requiring open reduction and those with concurrent elbow instability should be counseled about their increased risk of stiffness. The authors recommend initially attempting a closed reduction in high-risk patients to help mitigate the risk of postoperative stiffness. Early initiation of range of motion exercises may also be beneficial for at-risk patients. LEVEL OF EVIDENCE: Level III: Therapeutic studies-Investigating the results of treatment.

Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients.

BACKGROUND/OBJECTIVE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD. METHODS: Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment. RESULTS: The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients. CONCLUSIONS: These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.

Safety and tolerability of intravitreal umedaptanib pegol (anti-FGF2) for neovascular age-related macular degeneration (nAMD): a phase 1, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a single-dose intravitreal umedaptanib pegol (anti-FGF2, investigational new drug) for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: Nine participants who had a diagnosis of refractory nAMD were enrolled and received a single intravitreal injection of umedaptanib pegol at increasing doses of 0.2, 1.0 or 2.0 mg in the study eye. RESULTS: All three doses of umedaptanib pegol evaluated in the study were safe and well tolerated. No severe adverse event (AE) was observed in the study. There was an improvement in retinal fluid measured by central subfield thickness (CST) in most subjects. Remarkably, all three subjects who received 2.0 mg/eye showed improvement of more than 150 µm. CONCLUSIONS: Intravitreal umedaptanib pegol was safe, well tolerated, and demonstrated an indication of bioactivity in participants that have persistent subretinal fluid refractory to the treatment with anti-VEGFs.