Epigenomic profiling of the infrapatellar fat pad in osteoarthritis.

Osteoarthritis is a prevalent, complex disease of the joints, and affects multiple intra-articular tissues. Here, we have examined genome-wide DNA methylation profiles of primary infrapatellar fat pad and matched blood samples from 70 osteoarthritis patients undergoing total knee replacement surgery. Comparing the DNA methylation profiles between these tissues reveal widespread epigenetic differences. We produce the first genome-wide methylation quantitative trait locus (mQTL) map of fat pad, and make the resource available to the wider community. Using two-sample Mendelian randomization and colocalization analyses, we resolve osteoarthritis GWAS signals and provide insights into the molecular mechanisms underpinning disease aetiopathology. Our findings provide the first view of the epigenetic landscape of infrapatellar fat pad primary tissue in osteoarthritis.

Disentangling the detrimental effects of local from systemic adipose tissue dysfunction on articular cartilage in the knee.

OBJECTIVE: Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee. METHODS: Intra-articular adipose tissue development was studied using reporter mice. Mice with selective lipodystrophy of intra-articular adipose tissue were generated by conditional knockout (cKO) of Bscl2 in Gdf5-lineage cells, and compared with whole-body Bscl2 knockout (KO) mice with generalised lipodystrophy and associated systemic metabolic dysfunction. OA was induced by surgically destabilising the medial meniscus (DMM) and obesity by high-fat diet (HFD). Gene expression was analysed by quantitative RT-PCR and tissues were analysed histologically. RESULTS: The infrapatellar fat pad (IFP), in contrast to overlying subcutaneous adipose tissue, developed from a template established from the Gdf5-expressing joint interzone during late embryogenesis, and was populated shortly after birth by adipocytes stochastically arising from Pdgfrα-expressing Gdf5-lineage progenitors. While female Bscl2 KO mice with generalised lipodystrophy developed spontaneous knee cartilage damage, Bscl2 cKO mice with intra-articular lipodystrophy did not, despite the presence of synovial hyperplasia and inflammation of the residual IFP. Furthermore, male Bscl2 cKO mice showed no worse cartilage damage after DMM. However, female Bscl2 cKO mice showed increased susceptibility to the cartilage-damaging effects of HFD-induced obesity. CONCLUSION: Our findings emphasise the prevalent role of systemic metabolic and inflammatory effects in impairing cartilage homeostasis, with a modulatory role for intra-articular adipose tissue.

Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.

OBJECTIVE: Metabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular ß-adrenergic receptor (ßAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium. DESIGN: We used the ßAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia. RESULTS: Injured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice. CONCLUSIONS: Acute ßAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways.

Effect of isometric quadriceps exercise on local microcirculation of the infrapatellar fat pad in female patients with knee osteoarthritis.

OBJECTIVE: To elucidate the local microcirculation of the infrapatellar fat pad (IFP) in patients with knee osteoarthritis (KOA) by determining the changes in IFP hardness and hemoglobin concentration during isometric quadriceps exercise (IQE). DESIGN: In this observational cross-sectional study, patients diagnosed with bilateral KOA were included in the KOA group (30 knees), healthy older adults in the control group (20 knees), and younger adults in the young group (20 knees). Ultrasonography was performed at rest and during IQE to measure IFP hardness based on shear wave velocity. Near-infrared spectroscopy was performed to measure oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (cHb) in the IFP before (Baseline), during (IQE task), and after IQE (Post). IFP hardness and O2Hb, HHb, and cHb concentration were analyzed using a linear mixed model for the groups and measurement points. RESULTS: During IQE, IFP hardness changes were significantly less in the KOA group than in the other groups (KOA: 95 % confidence intervals (CIs) [-0.854, 0.028]; control: 95 % CI [-0.941, -0.341]; and young: 95 % CI [-2.305, -1.706]). In the KOA group, O2Hb concentration exhibited no significant changes at Post compared with Baseline; however, significant changes were observed in the other groups (KOA: 95 % CI [-1.176, 0.423]; control: 95 % CI [-1.452, -0.276]; and young: 95 % CI [-4.062, -2.102]). CONCLUSIONS: During IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP.

Nonpharmacologic rate control of postoperative atrial fibrillation in the canine sterile pericarditis model.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is common following open heart surgery, and is associated with significant morbidity. Medications used for ventricular rate control of POAF may not be effective in controlling rapid ventricular rates during the postoperative period because of increased sympathetic tone. The purpose of this study was to develop nonpharmacologic rate control of POAF by atrioventricular node (AVN) fat pad stimulation using clinically available temporary pacing wires in the canine sterile pericarditis model. METHODS: We studied 10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-3. The AVN fat pad stimulation (amplitude 2-15 mA; frequency 20 Hz; pulse width 0.03-0.2 ms) was performed during sustained POAF (>5 min). We measured ventricular rate and inefficient ventricular contractions during sustained POAF and compared it with and without AVN fat pad stimulation. Also, the parameters of AVN fat pad stimulation to achieve a rate control of POAF were measured over the postoperative days. RESULTS: Eleven episodes of sustained POAF were induced in 5/10 sterile pericarditis dogs in the closed-chest state on postoperative days 1-2. During POAF, the AVN fat pad stimulation decreased the ventricular rate from 178 ± 52 bpm to 100 ± 8 bpm in nine episodes. Nonpharmacologic rate control therapy successfully controlled the ventricular rate and eliminated inefficient ventricular contractions during POAF for the duration of the AVN fat pad stimulation. The AVN fat pad stimulation output remained relatively stable over the postoperative days. CONCLUSION: During sustained POAF, nonpharmacologic rate control by AVN fat pad stimulation effectively and safely controlled rapid ventricular rates throughout the postoperative period.

The suprapatellar fat pad: A histotopographic comparative study.

The suprapatellar fat pad is an adipose tissue located in the anterior knee whose role in osteoarthritis is still debated. Considering that anatomy drives function, the aim of this histotopographic study was to investigate the specific morphological features of the suprapatellar fat pad versus the infrapatellar fat pad in the absence of osteoarthritis, for a broad comparative analysis. Suprapatellar fat pad and infrapatellar fat pad tissue samples (n = 10/group) underwent microscopical/immunohistochemical staining and transmission electron microscopy analysis; thus, tissue-specific characteristics (i.e., vessels and nerve endings presence, lobuli, adipocytes features, septa), including extracellular matrix proteins prevalence (collagens, elastic fibers), were focused. Multiphoton microscopy was also adopted to evaluate collagen fiber orientation within the samples by Fast Fourier Transform (coherency calculation). The absence of inflammation was confirmed, and comparable counted vessels and nerve endings were shown. Like the infrapatellar fat pad, the suprapatellar fat pad appeared as a white adipose tissue with lobuli and septa of comparable diameter and thickness, respectively. Tissue main characteristics were also proved by both semithin sections and transmission electron microscopy analysis. The suprapatellar fat pad adipocytes were roundish and with a smaller area, perimeter, and major axis than that of the infrapatellar fat pad. The collagen fibers surrounding them showed no significant difference in collagen type I and significantly higher values for collagen type III in the infrapatellar fat pad group. Regarding the septa, elastic fiber content was statistically comparable between the two groups, even though more represented by the suprapatellar fat pad. Total collagen was significantly higher in the infrapatellar fat pad and comparing collagen type I and type III they were similarly represented in the whole cohort despite collagen type I appearing to be higher in the infrapatellar fat pad than in the suprapatellar fat pad and vice versa for collagen type III. Second harmonic generation microscopy confirmed through coherency calculation an anisotropic distribution of septa collagen fibers. From a mechanical point of view, the different morphological characteristics determined a major stiffness for the infrapatellar fat pad with respect to the suprapatellar fat pad. This study provides, for the first time, a topographic description of the suprapatellar fat pad compared to the infrapatellar fat pad; differences between the two groups may be attributed to a different anatomical location within the knee; the results gathered here may be useful for a more complete interpretation of osteoarthritis disease, involving not only cartilage but the whole joint.

The utility of Martius fat pad in the repair of urogenital fistulae: review of current evidence.

OBJECTIVE: To present the contemporary evidence on transvaginal urogenital fistulae (UGF) repair with Martius fat pad (MFP), compared to direct graftless fistula repair. METHODS: We reviewed all available studies reporting lower UGF repair via the transvaginal approach in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). The primary outcome of interest was the fistula closure rates. When available, patients' baseline characteristics, indications for surgery, and early and late postoperative complications with focus on MFP-related complications are reported. RESULTS AND DISCUSSION: In obstetric fistulae, tissue interposition has been almost completely abandoned, with contemporary large series reporting closure rates of >90% with graftless repair, even for complex fistulae. Similarly, most simple, non-irradiated iatrogenic fistulae can be closed safely without or with tissue interposition with success rates ranging between 86% and 100%. However, MFP is valuable in fistulae with difficulty achieving tension-free and layered closure, with significant tissue loss, urethral involvement and with poorly vascularised tissues after radiotherapy, with reported success rates between 80% and 97% in those challenging situations. CONCLUSION: A UGF repair should be individualised after considering the specific characteristics and complexity of the procedure. MFP interposition is probably unnecessary for the majority of low (obstetric) fistulae within otherwise healthy tissues. However, MFP may still have a place to maximise outcomes in low-income settings, in select cases with higher (iatrogenic) fistulae, and in most cases with radiotherapy.

Patellar height: an important parameter in knee MRI associated with tendinopathy, quadriceps fat pad edema (QFPE), anterior cruciate ligament mucoid degeneration (ACL-MD), and lateral cartilage damage.

BACKGROUND: Some pathologies associated with abnormal patellar height have been reported in the literature. However, its relationship with some pathologies, such as anterior cruciate ligament mucoid degeneration (ACL-MD) and focal cartilage defect, has not been investigated. PURPOSE: To investigate the relationship between patellar height with patellar-quadriceps tendinopathy, quadriceps fat pad edema, ACL-MD, and focal cartilage defect. MATERIAL AND METHODS: Magnetic resonance imaging of the knees of 261 patients were classified into three groups as normal, patella alta, and patella baja, and evaluated in terms of patellar-quadriceps tendinopathy, quadriceps fat pad edema, ACL-MD, and focal cartilage defect. RESULTS: There were 261 patients (140 men, 121 women; age range = 18-60 years; mean age = 30 ± 4.7 years). Of the 261 patients, 181 (69.3%) were normal, 56 (21.4%) were patella alta, and 24 were patella baja (9.1%). Patellar-quadriceps tendinopathy, quadriceps fat pad edema, and ACL-MD rates were significantly higher compared to the normal group (P <0.05). While a moderate positive correlation was found between patellar height shift and patellar-quadriceps tendinopathy and ACL-MD, there was a small correlation between patellar height shift and quadriceps fat pad edema. The rate of focal cartilage defect was significantly higher in the middle part of the lateral femoral condyle and lateral knee joint only in patella alta. CONCLUSION: The risk of patellar-quadriceps tendinopathy, quadriceps fat pad edema, ACL-MD, and lateral focal cartilage defect is higher in patients with alta-baja. The radiologist should evaluate these pathologies more carefully, especially subtle ones, in patients with abnormal patellar height.

Effect of weight loss on knee joint synovitis over 48 months and mediation by subcutaneous fat around the knee: data from the Osteoarthritis Initiative.

BACKGROUND: Obesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression. METHODS: We included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (< ± 3% change, n = 117) over 48 months matched for age and sex. In magnetic resonance imaging (MRI) at baseline and 48 months, effusion-synovitis and Hoffa-synovitis using the MRI Osteoarthritis Knee Score (MOAKS) and average joint-adjacent SCF (ajSCF) were assessed. Odds-ratios (ORs) for synovitis progression over 48 months (≥ 1 score increase) were calculated in logistic regression models adjusting for age, sex, baseline BMI, Physical Activity Scale for the Elderly (PASE), and baseline SCF measurements. Mediation of the effect of weight loss on synovitis progression by local SCF change was assessed. RESULTS: Odds for effusion-synovitis progression decreased with weight loss and ajSCF decrease (odds ratio [OR] = 0.61 and 0.56 per standard deviation [SD] change, 95% confidence interval [CI] 0.44, 0.83 and 0.40, 0.79, p = 0.002 and 0.001, respectively), whereas odds for Hoffa-synovitis progression increased with weight loss and ajSCF decrease (OR = 1.47 and 1.48, CI 1.05, 2.04 and 1.02, 2.13, p = 0.024 and 0.038, respectively). AjSCF decrease mediated 39% of the effect of weight loss on effusion-synovitis progression. CONCLUSIONS: Effusion-synovitis progression was slowed by weight loss and decrease in local subcutaneous fat. Hoffa-synovitis characterized by fluid in the infrapatellar fat pad increased at the same time, suggesting a decreasing fat pad rather than active synovitis. Decrease in local subcutaneous fat partially mediated the systemic effect of weight loss on synovitis.

A CCL2/MCP-1 antagonist attenuates fibrosis of the infrapatellar fat pad in a rat model of arthritis.

BACKGROUND: Fibrosis of the infrapatellar fat pad (IFP) is a feature of osteoarthritis and contributes substantially to the pain and dysfunction in patients' joints. However, the underlying mechanisms remain unclear. C-C motif chemokine ligand-2 (CCL2) plays a central role in tissue fibrosis. Thus, we aimed to investigate the role of CCL2 in the development of IFP fibrosis in a rat model of arthritis, hypothesizing that a CCL2 antagonist could mitigate fibrotic progression. METHODS: We induced arthritis in male Wistar rats using intra-articular injections of carrageenan. Furthermore, to evaluate the effects of a CCL2 antagonist on protein expression and collagen deposition in the IFP of the rats, we transferred an N-terminal-truncated CCL2 gene into a rat model via electroporation-mediated intramuscular injection. Macrophage infiltration and collagen deposition in the IFP were analyzed in vivo. Groups were compared using the Mann-Whitney U test and Student's t-test. RESULTS: We identified infiltrating macrophages as well as increases in CCL2 and TGF-ß levels as collagen deposition progressed. Gene transfer of the CCL2-antagonist before arthritis induction attenuated collagen deposition remarkably. CONCLUSIONS: We provide initial evidence that anti-CCL2 gene therapy can effectively suppress the development of IFP fibrosis in a rat model. Thus, targeting CCL2 holds promise as a therapeutic strategy for managing tissue fibrosis in osteoarthritis patients.

Dynamic ultrasound assessment for insertional achilles tendinopathy: the COcco-RIcci (CORI) sign.

OBJECTIVE: To describe a novel, dynamic ultrasound assessment of the Achilles tendon at the calcaneal insertion taking advantage of the effusion within the deep retrocalcaneal bursa as a natural contrast agent. MATERIALS AND METHODS: Positioning the ultrasound transducer in a longitudinal plane over the Achilles tendon at the calcaneal insertion, manual compression of the deep retrocalcaneal bursa can be performed using the other hand. Dynamically shifting the anechoic effusion from the proximal to the distal compartment of the bursa, the undersurface of the Achilles tendon is lifted from the underlying cortical bone of the superior facet of the calcaneal tuberosity. RESULTS: Pushing the anechoic effusion from the bursal cavity toward the undersurface of the Achilles tendon, an eventual focal injury of its deep fibers can be visualized dynamically during the maneuver as a "black crescent" within the tendon-i.e., the COcco-RIcci (CORI) sign. Otherwise, the gliding of the posteroinferior wedge of the Kager's fat pad inside the tendon-bone interface can be observed in normal conditions. CONCLUSION: The CORI sign is a novel sonographic sign to further enhance the diagnostic accuracy of dynamic ultrasound imaging in patients with insertional Achilles tendinopathy especially to detect focal injury involving the deep fibers of the tendon.

3D segmentation and quantitative analysis of age-related changes in the Hoffa fat pad using MRI.

The infrapatellar fat pad (IFP), also known as the Hoffa fat pad, is an essential structure in the knee joint with diverse functions and characteristics. Pathological changes in it can lead to anterior knee pain and impingement. The aim of this study was to investigate the relationship between age and Hoffa fat pad volume. A retrospective analysis was conducted on MRI scans of 100 individuals aged 10-80 years with no Hoffa fat pad pathology. The IFP was meticulously segmented on each sagittal and coronal MRI plane and its volume was calculated on the basis of the segmented boundaries. Correlation analysis was used to explore the relationships among age, sex, height, weight, and patella-related variables. Contrary to the hypothesis, there was no significant correlation between age and Hoffa fat pad volume. However, there were strong positive correlations between Hoffa fat pad volume and individuals' height, patellar height, and patellar ligament length. Multivariable linear regression analysis revealed that height, weight, patellar height, and patellar ligament length collectively explained 67% of Hoffa fat pad volume variability. These findings suggest that the Hoffa fat pad adapts to accommodate morphological changes in the knee joint as individuals grow taller. In conclusion, our study examined Hoffa fat pad volume in individuals across the age spectrum, using advanced imaging techniques to reveal the importance of considering height and knee-related variables for assessing Hoffa fat pad volume. This elucidates age-related volume changes and highlights the need for further research to understand its functional implications and interactions within the knee joint, with the aim of improving orthopedic interventions.

Volume Redistribution of the Buccal Fat Pad After Reduction Malarplasty.

BACKGROUND: During reduction malarplasty, cheek bulging could be found immediately after zygomatic complex is moved inwards, backwards and upwards. As patient is in the supine position during surgery, the effect of gravity is eliminated, so the only reason for the bulge is the redistribution of the soft tissue in the deep facial spaces. The buccal fat pad, with its main body behind the zygomatic arch and buccal extension in the cheek area, is most likely to be responsible for the bulge. METHODS: 3D buccal extension models were reconstructed from preoperative and long-term follow-up CT images and the volume measured. By comparing the pre- and postoperative 3D models, the shape deviation of the buccal extension and facial soft tissue can be identified. RESULTS: Eleven patients (22 buccal extensions) met the inclusion criteria. Compared with the preoperative buccal extension volume, the postoperative volume increased significantly. By comparing the reconstructed models, the buccal extension volume increase with anteroinferior protrusion can be visually detected, and cheek bulging was clearly identified on the lower face. The bulging area coincided with the projection of the buccal extension on the skin surface. CONCLUSIONS: Reduction malarplasty may cause volume redistribution of the buccal fat pad. Therefore, preoperative assessment of the size of the buccal fat pad based on CT images is recommended. The buccal extension volume increase with anteroinferior protrusion is an important cause of postoperative cheek bulging and should be considered during treatment. 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 .

Infra-patellar fat pad-derived mesenchymal stem cells maintain their chondrogenic differentiation potential after arthroscopic harvest with blood-product supplementation.

PURPOSE: Mesenchymal stem cells/medicinal signaling cells (MSCs) possess therapeutic potential and are used in regenerative orthopaedics. The infra-patellar fat pad (IFP) is partially resected during knee arthroscopy (KASC) and contains MSCs. Heat, irrigation, and mechanical stress during KASC may decrease MSC's therapeutic potential. This study assessed MSCs' regenerative potential after arthroscopic IFP harvest and potential effects of two blood products (BP) (platelet-rich plasma (PRP), hyperacute serum (HAS)) on MSCs' viability and chondrogenic differentiation capacity. METHODS: IFP was arthroscopically harvested, isolated, and counted (n = 5). Flow cytometry was used to assess cell viability via staining with annexin V/7-AAD and stemness markers via staining for CD90, CD73, and CD105. MSCs were incubated with blood products, and metabolic activity was determined via an XTT assay. Deposition of cartilage extracellular matrix was determined in histologic sections of chondrogenically differentiated 3D pellet cultures via staining with Alcian Blue. Expression of cartilage-specific genes (SOX9, MMP3/13, ACAN, COL1/2) was analyzed via quantitative PCR. RESULTS: MSC isolation from IFP yielded 2.66*106 ± 1.49*106 viable cells from 2.7 (0.748) g of tissue. MSC markers (CD 90/105/73) were successfully detected and annexin V staining showed 81.5% viable cells. XTT showed increased metabolic activity. Within the BP groups, this increase was significant (days 0-14, p < 0.05). PCR showed expression of cartilage-specific genes in each group. COL2 (p < 0.01) as well as ACAN (p < 0.001) expression levels were significantly higher in the HAS group. Histology showed successful differentiation. CONCLUSION: Arthroscopic harvest of IFP-MSCs yields sufficient cells with maintained regenerative potential and viability. Blood products further enhance MSCs' viability.

Advancements in Face and Neck Contouring: Integrating Radiofrequency-Assisted Liposuction with FaceTite and Buccal Fat Pad Excision for Facial Slimming.

BACKGROUND: The integration of neck liposuction with FaceTite Manipulus Radiofrequency (RF) technology and buccal fat pad excision for enhanced neck rejuvenation promise heightened precision and efficacy in sculpting the neck and jawline. Neck liposuction, coupled with RF technology, provides controlled thermal energy for adipose tissue treatment and collagen remodeling, while buccal fat pad excision offers refined contouring of the lower face and neck. This integrated approach aims to optimize patient outcomes and advance the field of esthetic plastic surgery. METHODS: A prospective study was conducted from 2016 to 2023 on 80 consecutive patients who presented to the author's private clinic and required neck remodeling surgery for esthetic purposes. Patients were monitored and clinic appointments were scheduled at intervals of 0, 1, 3, 6 and 12 months post-treatment for evaluation. A tape measure recorded submental length at 1 and 6 months, and a satisfaction survey was administered one week before surgery and after six months. Physicians assessed improvement using a five-point scale for patient satisfaction and a four-point scale for overall improvement. RESULTS: All patients underwent successful RFAL treatment, consistently achieving satisfaction with the outcomes. The average reduction in submental length measured 23 mm during the 6-month follow-up period. Additionally, the removal of buccal fat pads played a pivotal role in facial slimming and enhancing the esthetics of the upper cheek region. CONCLUSIONS: The integration of neck liposuction with FaceTite RF technology and buccal fat pad excision offers a promising approach for enhanced neck rejuvenation and facial contouring. This combined method demonstrates heightened precision and efficacy in sculpting the neck and jawline, aiming to optimize patient outcomes and advance the field of esthetic plastic surgery. 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 .

Temporal Augmentation Effect of Reduction Malarplasty: Application of our Bracing Technique with Zygomatic Arch Elevation.

BACKGROUND: A broad midface is usually accompanied by temporal depression. Traditional reduction malarplasty may visually improve the temporal depression by the inward reduction of zygomatic arch, but also has a high risk of soft tissue sagging. Our bracing technique has been reported to have an anti-sagging effect and may have a temporal augmentation effect as observed during our long-term clinical practice. METHODS: Data of patients who received reduction malarplasty with our bracing technique from September 2015 to July 2023 were retrospectively collected. The pre-op and post-op CT images of those who met the inclusion criteria were used for three-dimensional reconstruction and measurements of the thickness and volume of the temporal soft tissue as well as the elevation distance of zygomatic arch. RESULTS: Fifty-eight patients with an average follow-up of 18.4 ± 9.1 months were included. Despite mild thinning of the temporalis muscle after reduction malarplasty, the overall thickness of the temporal soft tissue significantly increased due to the significant thickening of the temporal adipose-fascial layer. There was a 0.5 ml-increase in the temporal volume although without statistical difference. No significant correlation was detected between the elevation distance of zygomatic arch and the temporal thickness or volume change. CONCLUSIONS: The bracing technique of reduction malarplasty not only plays an anti-sagging role, but also has a temporal augmentation effect through the superior bracing by the elevation and rigid fixation of the zygomatic arch. It adds brilliance to the traditional technique and can be suggested especially when the patients are disturbed by temporal depression. 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 .

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis.

Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells' (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.

Hoffa's fat pad resection during total knee arthroplasty does not affect functioning and gait: a double-blind randomized clinical trial.

INTRODUCTION: Hoffa's fat pad is considered a source of anterior knee pain and may limit prosthetic knee function. Resection of Hoffa's fat pad in total knee arthroplasty (TKA), however, is controversial, and little is known about the functional outcomes including gait quality. This double-blind randomized controlled trial (i) compared functional recovery between TKAs where Hoffa was resected or preserved, and (ii) compared recovery of self-reported function with objective (gait-related) outcomes. MATERIALS AND METHODS: Eighty-five patients (age 66.4 ± 8.0 years, 47% women) scheduled to undergo TKA for primary osteoarthritis were randomly assigned to either fat pad resection or preservation. Subjective measures of functioning were assessed at baseline, 6 weeks, 3 months, and 12 months postoperatively and included the Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala, and visual analog scale (VAS) for pain. Objective measures of functioning were assessed at baseline, 3 months, and 12 months postoperatively and included instrumented range-of-motion and gait analysis. Longitudinal analyses (generalized estimating equations) were used to compare recovery between groups, and chi-square tests compared attainment of minimal clinical important difference (MCID) and patient acceptable symptom state (PASS). Finally, correlation analyses explored associations between subjective and objective recovery in function. RESULTS: Resection patients showed poorer improvement in KOOS quality of life in the first 6 weeks (B=-10.02, 95% confidence interval (CI) [-18.91, -1.12], p = .027), but stronger improvement in knee extension after 3 months (B = 3.02, 95%CI [0.45, 5.60], p = .021) compared to preservation patients. Regarding MCID or PASS, no differences were noted between groups at 3 and 12 months (all p > .05). Subjective function substantially improved in the first 3 months, while objective outcomes improved only between 3 and 12 months. Moderate to strong correlations were identified between changes in knee flexion and gait with Kujala and KOOS in the resection but not in the preservation group. CONCLUSIONS: Similar functional outcomes were achieved after TKA with or without resection of Hoffa's fat pad. Hence, removing the fat pad to promote surgical exposure will not affect functional outcomes including gait quality. Functional recovery of objective outcomes was not always consistent with subjective recovery, suggesting that both self-reported as well as objective, gait-related outcomes may provide meaningful information on functional recovery following TKA. TRIAL REGISTRATION: This clinical trial was prospectively registered under the Netherlands Trial Registry (# NL3638). This registry has recently been replaced by the Dutch Trial Registry where this study can be accessed via https://onderzoekmetmensen.nl/en/trial/20994 .

Clinical and demographic predictors of buccal fat pad volume in thyroid eye disease.

PURPOSE: To understand how thyroid eye disease (TED) impacts buccal fat pad (BFP) volume. METHODS: In this cohort study, computed tomography (CT) scans and charts of adult patients with and without TED were obtained from an institutional database. The primary outcome was BFP volume in cubic centimeters. Three independent, blinded observers analyzed scans using Horos, a free, open-source medical image viewing software. Bivariate and multivariable analyses were performed. We determined sample size using an effect size based on published reports of the minimum amount of fat excision needed to notice a clinical difference. Equivalence testing against upper and lower bounds set by the same effect size was conducted to assess practical significance of the results. RESULTS: Our sample was sufficient to detect a difference as large as 1.5cc with 95% power. 72 scans were included in our study, 24 TED patients and 48 controls. Mean BFP volume was not statistically different between TED patients and controls (3.96 cc vs 4.06 cc, p = .778). Analysis of covariance adjusting for relevant patient factors (age, sex, and BMI) also failed to find a significant difference between groups. Equivalence testing was significant (p < .001) and revealed the observed difference between groups was less than any clinically meaningful difference. For an effect size of 1.5cc, the data suggests there is a 5% risk of a false negative. CONCLUSIONS: TED was not associated with a significant difference in BFP volume, suggesting that the BFP is spared from TED-related soft-tissue expansion.

Buccal fat pedicle flap with a delayed tarsoconjunctival flap for lower eyelid retraction: a new surgical methodology.

PURPOSE: The aim of this retrospective case review is to present a novel surgical technique used in the treatment of recalcitrant lower eyelid retraction. METHODS: This study was performed as a retrospective case review of 4 patients who have failed standard conservative surgical interventions for lower eyelid retraction repair. 3 patients developed lower eyelid retraction following surgical intervention for orbital trauma and 1 patient developed lower eyelid retraction in the setting of granulomatosis with polyangiitis. The surgical technique was identical in each patient and performed by an oculofacial plastic surgeon, sometimes together with an oral and maxillofacial surgeon. Follow-up results for all patients were assessed at 1 week, 1 month, and 3 months. RESULTS: All four patients demonstrated initial improvement in lower eyelid position, fullness, and height. A common finding was mild lateral postoperative entropion, which was easily overcome with an upper eyelid tarsoconjunctival flap. There were no surgical complications sustained in any of the cases. CONCLUSIONS: This retrospective case review provides a novel surgical option for the correction of recalcitrant lower eyelid retraction. The excellent vascularity provided by this flap, location, and easy access support its use. A prospective study comparing alternative solutions would be useful in comparing the buccal fat pad vascularized pedicle to alternative methods used to correct refractory and cicatricial lower eyelid retraction.