Decoding the muscle transcriptome of patients with late onset Pompe disease reveals markers of disease progression.

Late-onset Pompe Disease (LOPD) is a rare genetic disorder caused by the deficiency of acid alpha-glucosidase leading to progressive cellular dysfunction due to the accumulation of glycogen in the lysosome. The mechanism of relentless muscle damage - a classic manifestation of the disease - has been extensively studied by analysing the whole muscle tissue; however, little, if any, is known about transcriptional heterogeneity among nuclei within the multinucleated skeletal muscle cells. This is the first report of application of single nuclei RNA sequencing to uncover changes in the gene expression profile in muscle biopsies from eight patients with LOPD and four muscle samples from age and gender matched healthy controls. We matched these changes with histology findings using GeoMx Spatial Transcriptomics to compare the transcriptome of control myofibers from healthy individuals with non-vacuolated (histologically unaffected) and vacuolated (histologically affected) myofibers of LODP patients. We observed an increase in the proportion of slow and regenerative muscle fibers and macrophages in LOPD muscles. The expression of the genes involved in glycolysis was reduced, whereas the expression of the genes involved in the metabolism of lipids and amino acids was increased in non-vacuolated fibers, indicating early metabolic abnormalities. Additionally, we detected upregulation of autophagy genes, and downregulation of the genes involved in ribosomal and mitochondrial function leading to defective oxidative phosphorylation. The upregulation of the genes associated with inflammation, apoptosis and muscle regeneration was observed only in vacuolated fibers. Notably, enzyme replacement therapy - the only available therapy for the disease - showed a tendency to restore metabolism dysregulation, particularly within slow fibers. A combination of single nuclei RNA sequencing and spatial transcriptomics revealed the landscape of normal and the diseased muscle, and highlighted the early abnormalities associated with the disease progression. Thus, the application of these two new cutting-edge technologies provided insight into the molecular pathophysiology of muscle damage in LOPD and identified potential avenues for therapeutic intervention.

Guidelines for NGS procedures applied to prenatal diagnosis by the Spanish Society of Gynecology and Obstetrics and the Spanish Association of Prenatal Diagnosis.

OBJECTIVE: This document addresses the clinical application of next-generation sequencing (NGS) technologies for prenatal genetic diagnosis and aims to establish clinical practice recommendations in Spain to ensure uniformity in implementing these technologies into prenatal care. METHODS: A joint committee of expert obstetricians and geneticists was created to review the existing literature on fetal NGS for genetic diagnosis and to make recommendations for Spanish healthcare professionals. RESULTS: This guideline summarises technical aspects of NGS technologies, clinical indications in prenatal setting, considerations regarding findings to be reported, genetic counselling considerations as well as data storage and protection policies. CONCLUSIONS: This document provides updated recommendations for the use of NGS diagnostic tests in prenatal diagnosis. These recommendations should be periodically reviewed as our knowledge of the clinical utility of NGS technologies, applied during pregnancy, may advance.

Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle.

It is controversial whether mitochondrial dysfunction in skeletal muscle is the cause or consequence of metabolic disorders. Herein, we demonstrate that in vivo inhibition of mitochondrial ATP synthase in muscle alters whole-body lipid homeostasis. Mice with restrained mitochondrial ATP synthase activity presented intrafiber lipid droplets, dysregulation of acyl-glycerides, and higher visceral adipose tissue deposits, poising these animals to insulin resistance. This mitochondrial energy crisis increases lactate production, prevents fatty acid ß-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle accumulation of acetyl-CoA leads to acetylation-dependent inhibition of mitochondrial respiratory complex II enhancing oxidative phosphorylation dysfunction which results in augmented ROS production. By screening 702 FDA-approved drugs, we identified edaravone as a potent mitochondrial antioxidant and enhancer. Edaravone administration restored ROS and lipid homeostasis in skeletal muscle and reinstated insulin sensitivity. Our results suggest that muscular mitochondrial perturbations are causative of metabolic disorders and that edaravone is a potential treatment for these diseases.

Requested a Different Doctor: Developing and Evaluating an OSCE Assessing Core Skills in Supporting Trainees Facing Patient Discrimination.

BACKGROUND: Suboptimal support for colleagues experiencing discrimination can adversely impact clinician well-being and patient care. AIM: To describe resident performance and experience during an Objective Structured Clinical Examination (OSCE) case centered on supporting a trainee facing discrimination to inform enhanced, supportive learning environments. SETTING: Formative, internal medicine OSCE at a simulation center. PARTICIPANTS: 148 second-year residents across 2018, 2019, 2021, 2022. PROGRAM DESCRIPTION: Residents had 10 min to support a Muslim standardized intern (SI) experiencing discrimination from a patient. The SI rated resident performance across Supervision, Relationship Development, and Support domains and provided written feedback. Post-OSCE evaluations elicited resident reflections on case challenges. PROGRAM EVALUATION: Proficient residents (≥ 80% average score across domains, n = 85) performed better in all items, except in not acting defensive and collaborating with SI to develop follow-up plan, compared to non-proficient residents (n = 65). The SI described effective approaches to feeling supported, including using empathetic statements, stating personal stance on discrimination, exhibiting supportive body language, and verbalizing support. Stating knowledge of situation upfront was an area of improvement. Residents found engaging the distressed SI difficult. DISCUSSION: Use of an explicit discrimination OSCE case can help identify effective approaches to supporting targets of discriminatory patients to inform future training.

Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.

It is increasingly apparent that cancer cells, in addition to remodelling their metabolism to survive and proliferate, adapt and manipulate the metabolism of other cells. This property may be a telling sign that pre-clinical tumour metabolism studies exclusively utilising in-vitro mono-culture models could prove to be limited for uncovering novel metabolic targets able to translate into clinical therapies. Although this is increasingly recognised, and work towards addressing the issue is becoming routinary much remains poorly understood. For instance, knowledge regarding the biochemical mechanisms through which cancer cells manipulate non-cancerous cell metabolism, and the subsequent impact on their survival and proliferation remains limited. Additionally, the variations in these processes across different cancer types and progression stages, and their implications for therapy, also remain largely unexplored. This study employs an interdisciplinary approach that leverages the predictive power of mathematical modelling to enrich experimental findings. We develop a functional multicellular in-silico model that facilitates the qualitative and quantitative analysis of the metabolic network spawned by an in-vitro co-culture model of bone marrow mesenchymal stem- and myeloma cell lines. To procure this model, we devised a bespoke human genome constraint-based reconstruction workflow that combines aspects from the legacy mCADRE & Metabotools algorithms, the novel redHuman algorithm, along with 13C-metabolic flux analysis. Our workflow transforms the latest human metabolic network matrix (Recon3D) into two cell-specific models coupled with a metabolic network spanning a shared growth medium. When cross-validating our in-silico model against the in-vitro model, we found that the in-silico model successfully reproduces vital metabolic behaviours of its in-vitro counterpart; results include cell growth predictions, respiration rates, as well as support for observations which suggest cross-shuttling of redox-active metabolites between cells.

Anoctamin-5 related muscle disease: clinical and genetic findings in a large European cohort.

Anoctamin-5 related muscle disease is caused by biallelic pathogenic variants in the anoctamin-5 gene (ANO5) and shows variable clinical phenotypes: limb-girdle muscular dystrophy type 12 (LGMD-R12), distal muscular dystrophy type 3 (MMD3), pseudometabolic myopathy or asymptomatic hyperCKaemia. In this retrospective, observational, multicentre study we gathered a large European cohort of patients with ANO5-related muscle disease to study the clinical and genetic spectrum and genotype-phenotype correlations. We included 234 patients from 212 different families, contributed by 15 centres from 11 European countries. The largest subgroup was LGMD-R12 (52.6%), followed by pseudometabolic myopathy (20.5%), asymptomatic hyperCKaemia (13.7%) and MMD3 (13.2%). In all subgroups, there was a male predominance, except for pseudometabolic myopathy. Median age at symptom onset of all patients was 33 years (range 23-45 years). The most frequent symptoms at onset were myalgia (35.3%) and exercise intolerance (34.1%), while at last clinical evaluation most frequent symptoms and signs were proximal lower limb weakness (56.9%) and atrophy (38.1%), myalgia (45.1%) and atrophy of the medial gastrocnemius muscle (38.4%). Most patients remained ambulatory (79.4%). At last evaluation, 45.9% of patients with LGMD-R12 additionally had distal weakness in the lower limbs and 48.4% of patients with MMD3 also showed proximal lower limb weakness. Age at symptom onset did not differ significantly between males and females. However, males had a higher risk of using walking aids earlier (P = 0.035). No significant association was identified between sportive versus non-sportive lifestyle before symptom onset and age at symptom onset nor any of the motor outcomes. Cardiac and respiratory involvement that would require treatment occurred very rarely. Ninety-nine different pathogenic variants were identified in ANO5 of which 25 were novel. The most frequent variants were c.191dupA (p.Asn64Lysfs*15) (57.7%) and c.2272C>T (p.Arg758Cys) (11.1%). Patients with two loss-of function variants used walking aids at a significantly earlier age (P = 0.037). Patients homozygous for the c.2272C>T variant showed a later use of walking aids compared to patients with other variants (P = 0.043). We conclude that there was no correlation of the clinical phenotype with the specific genetic variants, and that LGMD-R12 and MMD3 predominantly affect males who have a significantly worse motor outcome. Our study provides useful information for clinical follow up of the patients and for the design of clinical trials with novel therapeutic agents.

Magnetic resonance spectroscopy in MELAS syndrome: correlation with CSF and plasma metabolite levels and change after glutamine supplementation.

PURPOSE: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. METHODS: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. RESULTS: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). CONCLUSION: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.

Genetic diagnosis of Duchenne and Becker muscular dystrophy through mRNA analysis: new splicing events.

BACKGROUND: Up to 7% of patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) remain genetically undiagnosed after routine genetic testing. These patients are thought to carry deep intronic variants, structural variants or splicing alterations not detected through multiplex ligation-dependent probe amplification or exome sequencing. METHODS: RNA was extracted from seven muscle biopsy samples of patients with genetically undiagnosed DMD/BMD after routine genetic diagnosis. RT-PCR of the DMD gene was performed to detect the presence of alternative transcripts. Droplet digital PCR and whole-genome sequencing were also performed in some patients. RESULTS: We identified an alteration in the mRNA level in all the patients. We detected three pseudoexons in DMD caused by deep intronic variants, two of them not previously reported. We also identified a chromosomal rearrangement between Xp21.2 and 8p22. Furthermore, we detected three exon skipping events with unclear pathogenicity. CONCLUSION: These findings indicate that mRNA analysis of the DMD gene is a valuable tool to reach a precise genetic diagnosis in patients with a clinical and anatomopathological suspicion of dystrophinopathy that remain genetically undiagnosed after routine genetic testing.

Expanding the phenotypic spectrum of TRAPPC11-related muscular dystrophy: 25 Roma individuals carrying a founder variant.

BACKGROUND: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined muscle disorders. TRAPPC11-related LGMD is an autosomal-recessive condition characterised by muscle weakness and intellectual disability. METHODS: A clinical and histopathological characterisation of 25 Roma individuals with LGMD R18 caused by the homozygous TRAPPC11 c.1287+5G>A variant is reported. Functional effects of the variant on mitochondrial function were investigated. RESULTS: The c.1287+5G>A variant leads to a phenotype characterised by early onset muscle weakness, movement disorder, intellectual disability and elevated serum creatine kinase, which is similar to other series. As novel clinical findings, we found that microcephaly is almost universal and that infections in the first years of life seem to act as triggers for a psychomotor regression and onset of seizures in several individuals with TRAPPC11 variants, who showed pseudometabolic crises triggered by infections. Our functional studies expanded the role of TRAPPC11 deficiency in mitochondrial function, as a decreased mitochondrial ATP production capacity and alterations in the mitochondrial network architecture were detected. CONCLUSION: We provide a comprehensive phenotypic characterisation of the pathogenic variant TRAPPC11 c.1287+5G>A, which is founder in the Roma population. Our observations indicate that some typical features of golgipathies, such as microcephaly and clinical decompensation associated with infections, are prevalent in individuals with LGMD R18.

Sex Differences in Transthyretin Cardiac Amyloidosis: Unraveling the Complexities in Epidemiology, Pathophysiology, Diagnosis, and Treatment.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterised by the deposition of transthyretin amyloid fibrils in the heart. ATTR-CA affects both men and women although there is evidence of sex differences in prevalence and clinical presentation. PURPOSE OF REVIEW: This review paper aims to comprehensively examine and synthesise the existing literature on sex differences in ATTR-CA. RECENT FINDINGS: The prevalence of ATTR-CA is higher in males although the male predominance is more apparent in older patients in the wild type form and in TTR genetic variants that predominantly result in a cardiac phenotype in the hereditary variant. Women tend to have less left ventricular hypertrophy (LVH) and a higher ejection fraction at clinical presentation which may contribute to a later diagnosis although the prognosis appears to be similar in both sexes. Female sex is a predictor of a good response to tafamidis 20 mg in TTR polyneuropathy but otherwise there are no data on sex differences in the efficacy of other treatments for ATTR-CA. It is crucial to define specific sex differences in ATTR-CA. A lower cut-off value for LVH in women may be needed to improve diagnosis. It is necessary to increase female representation in clinical trials to better understand possible sex differences in therapeutic management.

Resolving the Controversy Surrounding the Function of the Corrugator Supercilii Muscle.

INTRODUCTION: The corrugator supercilii muscle (CSM) has traditionally been recognized as a primary depressor of the eyebrows, playing a key role in expressing negative emotions and contributing to the formation of glabellar lines. However, recent studies indicate that the CSM may exhibit movements contrary to those previously documented, suggesting a more complex functional role. This research re-evaluates the anatomical and functional roles of the CSM and discusses their implications for botulinum toxin treatments. MATERIAL AND METHODS: A prospective, intrapersonal comparative, and split-face study was conducted over a five-year period, from January 6, 2019, to January 6, 2024, involving 298 patients who underwent botulinum toxin injections. The study divided participants into seven groups, each targeting specific anatomical areas of the CSM and associated muscles. Injection techniques were varied to assess their impact on brow dynamics, with outcomes measured by changes in eyebrow position and expression lines. RESULTS: The study demonstrated that targeting specific portions of the CSM and depressor supercilii muscle (DSM) leads to distinct outcomes in brow elevation and the reduction of expression lines. However, this approach was also frequently associated with the development of omega-shaped wrinkles. Split-face evaluations further validated that the modified injection techniques achieved superior eyebrow elevation compared to traditional methods. CONCLUSION: This study challenges the traditional view of the CSM as primarily a brow depressor, highlighting its role in medial brow elevation. These findings underscore the need for a nuanced approach in esthetic medicine, particularly in botulinum toxin injections, to achieve balanced and natural facial expressions. Understanding the full range of CSM functions is crucial for optimizing esthetic outcomes and enhancing patient satisfaction. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Role of Hyperbaric Oxygen in Filler-Induced Vascular Occlusion.

INTRODUCTION: The rising incidence of filler-induced vascular complications in the context of aesthetic procedures necessitates a thorough assessment of therapeutic options. Hyperbaric oxygen therapy (HBOT) has emerged as a potential intervention for filler-induced vascular occlusion (FIVO), although optimal dosing and timing remain undefined. METHODS: This review explores the pathophysiology of FIVO and elucidates HBOT's multifaceted role in salvaging ischemic tissue. The physical and biochemical mechanisms of HBOT, including its vasodilatory, anti-spasmodic, and anti-inflammatory effects, are examined. RESULTS: HBOT serves as an adjunctive therapy in FIVO management, emphasizing timely intervention, adherence to specific pressures (two atmosphere absolute), and session durations (60 minutes) to optimize efficacy and minimize complications. While existing HBOT protocols for compromised grafts provide insights, standardized guidelines for FIVO are lacking. CONCLUSION: HBOT enhances tissue oxygenation, modulates reactive oxygen species, and influences angiogenesis and hypoxia response. However, it does not replace key treatment protocols for filler vascular complications. Further research and standardized protocols are warranted to define HBOT's definitive role in mitigating filler-induced vascular complications. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Hybrid Filler Technique: A 5-Year Retrospective Analysis.

BACKGROUND: The combination of calcium hydroxylapatite (CaHA) and hyaluronic acid fillers (CPM-HA, cohesive polydensified matrix-based hyaluronic acid fillers, Belotero® range, Merz Pharmaceuticals GmbH, Frankfurt, Germany), known as hybrid fillers, has emerged as a popular approach in aesthetic medicine. Premixed CaHA with CPM-HA offers several advantages, including enhanced tissue elevation and reduced early volume loss after injection. OBJECTIVE: The objective of the present study is to assess the safety of premixing CaHA and CPM-HA fillers for rejuvenation purposes or as an aesthetic harmonization treatment. METHODS: This retrospective study presents the clinical experience of two expert injectors who consistently used premixed CaHA and CPM-HA fillers for aesthetic treatments between March 2018 and December 2023. The premixed hybrid formulation was standardized and administered following a published protocol. A total of 2112 patients were treated, with meticulous follow-up over a minimum of one year. RESULTS: In the 2112 patients treated, only 5 minor adverse events (0.24%) were reported. The adverse events consisted of 4 non-inflammatory nodules of which 2 completely resolved with hyaluronidase, and 1 case of transient edema. Secondary findings consist of the treated areas, type of CPM-HA used and mixing ratios that were applied. CONCLUSION: The results from the current retrospective study, with the largest published cohort so far, are consistent with prior publications and strongly support a good safety profile of the CaHA:CPM-HA hybrid blend. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reduced Injection Site Pain with Altered pH in 24-h Reconstituted Botulinum Toxin: Findings from a Randomized Controlled Study on Cosmetic Applications.

BACKGROUND: Botulinum toxin (BTX) injections are widely recognized for many cosmetic applications, but still commonly encounter a challenge: injection site pain (ISP). This discomfort can impact the overall patient experience and satisfaction, highlighting a need for innovative solutions to this problem. OBJECTIVE: This randomized controlled study aimed to determine whether adjusting the pH levels in a 24-h reconstituted botulinum toxin can serve as a strategy to mitigate ISP. METHODS: A controlled trial involving 24 volunteers was executed. Participants received incobotulinum toxin A. One side of each participant's face was treated with fresh toxin, while the other received a 24-h reconstituted version. Pain perceptions post-injection were assessed using the visual analogue scale (VAS). RESULTS: pH values of the fresh toxin were more acidic (6.17) than the 24-h reconstituted toxin (7.17). Out of 24 patients, 13 reported reduced ISP with the 24-h reconstituted toxin. The mean VAS score for the fresh toxin was 5.92, in contrast to 4.17 for the reconstituted toxin, indicating a significant difference (p<0.01). CONCLUSION: Limitations include the use of a VAS and a relatively small sample size. Altering the pH of BTX demonstrates potential in ISP reduction. However, broader, large-scale investigations are important for comprehensive validation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Updated Filler Emergency Kit: Next-Generation Emergency Solution.

INTRODUCTION: The rising popularity of facial filler injections has corresponded with an increase in reported complications. While a filler emergency kit was previously introduced, advancements in the field have highlighted certain limitations, prompting the development of the updated filler emergency kit (UFEK). METHODS: The authors conducted literature research up to February 2023, focusing on PubMed and open web searches for articles referred to filler emergent complications: vascular occlusion, blindness and anaphylaxis. Approximately 1200 articles were obtained from PubMed and other sources, and 45 articles were reviewed. RESULTS: The developed UFEK protocol delineates specific interventions meticulously tailored to address diverse emergent scenarios linked to soft tissue fillers complications. This protocol emphasizes the urgent requirement for timely and personalized interventions. CONCLUSION: The UFEK offers a standardized, comprehensive and effective approach. This work contributes to the responsible and informed progression of the field of aesthetic medicine, providing more value and safety, both for clinicians and patients. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Temporary Delayed Hypersensitivity Reaction to Botulinum Toxin-A After COVID-19 Vaccination: A Case Series.

PURPOSE: The occurrence of a hypersensitivity reaction with the injection of botulinum toxin type A (BTX-A) in cosmetic use is a rare complication. We report the largest case series of temporary delayed hypersensitivity reaction (DHR) with BTX-A following COVID-19 vaccination and the first cases to incobotulinum toxin A (incoBTX-A). METHODS: A retrospective multicentric case series of patients who developed a DHR to BTX-A after COVID-19 vaccination. RESULTS: Twelve patients were treated with BTX-A injections for the management of facial rhytids. The age range was between 29 and 45 years. Ten (83.3%) were female. Ten (83.3%) patients received incoBTX-A, and two received onabotulinum toxin A (onaBTX-A). All patients had COVID-19 vaccination (mRNA vaccine) between 1 and 7 months before. Within an average time of 24 h after BTX-A injection, all patients developed progressive facial swelling and erythema that were more prominent at the injection points. Intradermal allergic tests to BTX-A were performed in six (50%) patients, and the results were all negative. Adequate clinical control was achieved with systemic corticosteroids and antihistamines. After 1 year with no further vaccination, a new BTX-A treatment (provocation test) was performed in all patients with no secondary effects. CONCLUSION: Previous COVID-19 vaccination and the absence of new adverse events with further BTX-A injections suggest a temporary DHR. Clinicians should be aware of the importance of immunization history and its potential post-vaccine immunogenic effects with BTX-A. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Jawline Sharp Contouring With Hybrid Filler.

BACKGROUND: Having a well-defined jawline is a sign of youth and attractiveness among both men and women. Soft tissue fillers, such as calcium hydroxylapatite (CaHA) and hyaluronic acid (HA) fillers, offer nonsurgical alternatives for rejuvenating the lower face and enhancing the jawline. The aim of this study was to investigate the use of a premixed combination of HA with cohesive polydensified matrix technology (CPM, Belotero Intense, CPM-I) and CaHA to create a sharply defined jawline. METHODS: A total of 126 patients were enrolled in the study and treated with a premixed combination of CPM-I and CaHA using a retrograde fanning injection technique with cannulas. The injection volumes and product ratios were customized according to the patients' needs. RESULTS: The cohort consisted of 75 females and 51 males. The average injected volume of premixed CaHA:CPM-I was 5.83 mL. In the majority of patients, a 1:1 syringe ratio of CaHA:CPM-I was applied (n = 81, 64.2%). No adverse events were reported during the 6-month follow-up period. CONCLUSION: The hybrid filler approach investigated in this study shows promise for achieving well-defined, long-lasting jawline contours. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Premaxillary Graft with Costal Cartilage in Rhinoplasty: A Technique to Support the Nasal Tip.

BACKGROUND: Rhinoplasty is an ever-evolving field, with innovative techniques continually being developed to enhance both aesthetic and functional outcomes for patients. Increasingly, research has focused on the integral role of the facial skeleton in providing nasal support and projection. Central to the structural integrity of the nose is the maxillary bone, which occupies a pivotal position in the midface. METHODS: The objective of this study is to assess the outcomes of patients who underwent rhinoplasty involving the placement of a premaxillary graft fashioned from costal cartilage. The study aims to evaluate the graft's tolerance, stability, and potential complications. The patient cohort comprised individuals who underwent open approach rhinoplasty with premaxillary insufficiency, necessitating the placement of a costal cartilage graft anterior to the nasal spine, performed by the same surgeon between 2021 and 2022. A total of 38 patients, consisting of 5 men and 33 women aged between 18 and 58 years, were operated on during this period. RESULTS: Consistent maintenance of tip support was observed across all cases. Among the 33 patients, 20 were randomly chosen for a comparative assessment of the nasolabial angle in preoperative and postoperative profile photographs, demonstrating a statistically significant improvement. No complications such as graft displacement, scarring, extrusion, or infections were reported. CONCLUSION: The use of a premaxillary graft with costal cartilage appears to be a viable, well-tolerated option with favorable long-term outcomes. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hand Rejuvenation with Customizable Hybrid Fillers: Premixed Calcium Hydroxyapatite and Hyaluronic Acid.

INTRODUCTION: Hand aging is a prevalent concern characterized by the atrophy of local soft tissues and increased visibility of vessels and tendons. Hyaluronic acid (HA) and calcium hydroxyapatite (CaHA) are well-established treatments for addressing this issue. While hybrid filler containing HA and CaHA has been proposed for facial rejuvenation, studies investigating its efficacy for hand rejuvenation are lacking. OBJECTIVE: This study aims to assess the safety and efficacy of a premixed hybrid filler containing calcium hydroxyapatite (CaHA) and hyaluronic acid (HA) for hand rejuvenation. METHODS: A prospective, double-blind, controlled trial was conducted. The control arm (CA) received conventional subdermal treatment with CaHA at a 1:1 dilution. The intervention arm (IA) underwent hybrid treatment, consisting of CaHA at a 1:1 dilution combined with 1 ml of low-density HA. Evaluation was performed subjectively using the Global Aesthetic Improvement Scale (GAIS) and the Manchester Hand Grading System (MHGS), and objectively using cutometry, corneometry, and ultrasound. RESULTS: Both the CA and the IA exhibited high rates of patient satisfaction and satisfaction as assessed by blinded evaluators. Although numerical superiority was observed in the IA, no statistical difference was found between the two groups. Significant improvements in hydration, elasticity, and skin thickness were observed in both arms, with no discernible difference between them. Greater ultrasound echogenicity was noted in the IA, which, as indicated by existing literature, may suggest enhanced biostimulation. No adverse effects were reported in either arm. CONCLUSION: Premixed filler containing HA and CaHA for hand rejuvenation appears to be a safe and effective approach. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Attitudes Toward Implicit Bias Among Athletic Trainers.

Implicit biases are attitudes, emotions, or stereotypes that occur in an unconscious manner and have the potential to negatively affect behaviors, actions, and decisions. Recent studies have suggested that even when certain factors are controlled for, health care workers do not provide equitable care to patients from different demographics. When patients are not receiving equitable health care, there is a potential for disparities in patient-related outcomes. The purpose of this study was to determine attitudes toward implicit bias among athletic trainers. A secondary purpose of this study was to assess differences and correlations between attitudes toward implicit bias and demographic factors including age, years of experience, gender identity, sexual orientation, and race. Participants were recruited for this study by emailing athletic trainers from publicly available staff directories at institutions of higher education and high schools, and athletic training education program directors. The survey consisted of questions gathering demographic information and questions taken from the Attitudes Toward Implicit Bias Instrument. A total of 218 athletic trainers (age = 38 [11] y, years of certified experience = 14 [11] y) opened and completed the survey. On average, participants scored 71.0 [11.2] on the Attitudes Toward Implicit Bias Instrument. This mean score indicated that the average participant felt that implicit bias had the potential to negatively impact patient care and needed to be addressed through education. There was a significant, negligible negative correlation between age and attitudes toward implicit bias (r[216] = -.157, P = .02). Examining implicit bias among athletic trainers warrants further research to understand how implicit bias can negatively affect access to equitable health care opportunities. The development of high-quality interventions for identifying and addressing implicit bias is crucial to ensuring optimal patient outcomes in athletic training and all medical settings.