Are short term outcomes superior following total knee arthroplasty when infra-patellar fat pad is resected? A systematic review and meta-analysis.

BACKGROUND: Data suggests the infra-patellar fat pad (IPFP) is resected in the majority of total knee arthroplasty cases. Current literature suggests there may be scope for increasing preservations rates. A systematic review and meta-analysis of available literature was performed to assess if resection of IPFP resulted in superior patient outcomes. METHODS: Scopus, PubMed, Cochrane, Embase and CINAHL were systematically searched in February 2024 for articles of relevance and meta-analysis conducted. A standardized mean difference and confidence interval of 95% was calculated. An odds ratio was calculated for all included datasets. Heterogeneity was assessed for using the I2 statistic. RESULTS: Thirteen studies were included within this review. IPFP resection shortened the patella tendon at 6 months post-operatively (OR, 0.07; 95% CI, 0.02-0.12, P = 0.006). Results favoured preservation at 12 months post-operatively (OR, 0.02; 95% CI, -0.02 to 0.06, P = 0.32). Oxford Knee Society (OKS) results statistically favoured preservation at 6 months (OR, 1.57; 95% CI, 0.74-2.39, P = 0.0002). Findings at 12 months favoured resection (OR, -0.49; 95% CI, -5.39, 4.41, P = 0.84). Resection increased anterior knee pain at 6-12 months post-operatively (OR, 1.45; 95% CI, 1.12-1.89, P = 0.005). Combined subgroup analysis of flexion favoured resection (OR, -2.15; 95% CI, -6.52 to 2.22, P = 0.34). CONCLUSION: OKS and patella tendon length results favoured preservation at 6 months however did not reach minimal clinically important difference. Combined subgroup analysis of flexion did not yield a statistically significant result. Rates of anterior knee pain at 6-12 months favoured preservation.

Interobserver agreement and diagnostic challenges of Congo red staining for amyloid detection on fat pad aspiration biopsies.

INTRODUCTION: Congo red staining of fat pad fine needle aspiration specimens is a method utilized for evaluation of amyloid deposition. However, these specimens can pose diagnostic challenges for cytopathologists. As part of ongoing internal quality improvement measures, the objective of this study was to evaluate the intradepartmental interobserver agreement of these specimens and to identify factors that affect the variability of the interpretations. MATERIALS AND METHODS: There were 7 participants, which included 3 trainees, 3 cytopathologists, and 1 cytotechnologist. Each participant reviewed 50 Congo red stained fat pad fine needle aspiration slides. The interpretations were categorized into 3 groups: negative, indeterminate/suspicious, and positive. The participants also noted any interpretation challenges they encountered for each case. RESULTS: There was only slight interobserver agreement among all participants (κ = 0.133). Stratified by participant group, the interobserver agreement among the trainees was slight bordering on poor (κ = 0.028) and among cytopathologists was fair (κ = 0.249). The highest agreement between 2 observers was between 2 cytopathologists and the level of agreement was moderate bordering on fair (κ = 0.426). There were only 3 cases (6.0%) with full agreement among observers, while in 25 cases (50.0%), there were 2 category differences in interpretations. The primary diagnostic challenge reported by participants was when weak or focal birefringence was encountered as well as cases complicated by poor stain quality and overstaining. CONCLUSIONS: We found only slight interobserver agreement among all study participants. A major area of challenge was cases with weak birefringence resulting in high variance of interpretation among participants.

Surgical sealant using free pericardial fat pad with fibrin glue and polyglycolic acid sheets for secondary spontaneous pneumothorax: a novel technique.

We report on the "Triple-FP technique," a novel surgical approach for secondary spontaneous pneumothoraces, which combines a free pericardial fat pad, fibrin glue, and polyglycolic acid sheets. In our experience with 13 patients suffering from secondary spontaneous pneumothoraces, this method effectively prevented postoperative air leaks and re-operations. The technique includes the following steps: (1) harvesting free pericardial fat; (2) suturing around the lung parenchymal defect with the needles and thread left outside the thoracic cavity; (3) ensuring contact between the mediastinal pleural side of the fat and the lung; (4) applying fibrin glue to both the lung and fat before suturing; (5) securing the fat to the lung via the suture thread, reinforced with fibrin glue; and (6) stabilization with polyglycolic acid sheets and additional fibrin glue. This innovative technique is a reliable and effective treatment strategy for secondary spontaneous pneumothoraces, especially for patients with fragile lung tissue.

A Novel Infrapatellar Fat Pad Preservation Technique in Total Knee Arthroplasty Reduced Postoperative Pain and Wound Complications.

OBJECTIVE: The management of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains controversial. This study aimed to evaluate a novel IPFP preservation technique-"the medially pedicled IPFP flap"-for reducing postoperative pain, wound complications, and improving functional recovery after TKA. METHODS: A retrospective analysis was conducted on TKA cases at our institution from 2018 to 2021, including those with IPFP preservation (medially pedicled flap) versus IPFP complete resection. Patient demographics, perioperative parameters (blood loss, operative time, length of hospital stay, visual analogue scale [VAS] score, white cell count [WBC], C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and wound oozing), and postoperative follow-up data (VAS, Knee Society [KSS], or Knee Society functional assessment [KSFA] scores) were compared between groups. Independent sample t-tests were used to compare continuous data and chi-squared tests were used to compare categorical data between groups. RESULTS: Six hundred thirty patients were included, with 278 in the medial pedicled IPFP flap group (preservation group) and 352 in the IPFP resection group (resection group). The operative time was significantly shorter in the preservation versus resection group (125.5 ± 23.2 vs 130.3 ± 28.7 mins, p = 0.03), as was the length of hospital stay (8.4 ± 2.7 vs 9.2 ± 2.3 days, p < 0.01). Regarding pain, the preservation group had significantly lower VAS scores on postoperative day 2 (2.0 ± 0.8 vs 2.4 ± 1.2, p < 0.001) and day 3 (1.5 ± 0.5 vs 1.8 ± 1.0, p < 0.001). CRP and ESR levels on postoperative day 5 were also significantly lower in the preservation group. Wound oozing rates were significantly lower in the preservation versus resection group (0.7% vs 2.8%, p = 0.04). No significant differences existed in VAS, KSS, or KSFA scores at the last follow-up. CONCLUSION: The novel IPFP preservation technique significantly improved surgical exposure, shortened operative time and length of hospital stay. It also reduced wound pain and oozing compared to IPFP resection.

Therapeutic potential of dedifferentiated fat cells in a rat model of osteoarthritis of the knee.

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin. Methods: In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 106 DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of PTGS2, TNFAIP6, PRG4, BMP2, and BMP6 under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of ADAMTS4 and IL-6 were evaluated. Results: Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as PTGS2, TNFAIP6, and BMP2, under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of ADAMTS4 and IL6 in synovial fibroblasts. Conclusions: The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment.

Removal of the infrapatellar fat pad and associated synovium benefits female guinea pigs in the Dunkin Hartley model of idiopathic osteoarthritis.

Background: Several tissues contribute to the onset and advancement of knee osteoarthritis (OA). One tissue type that is worthy of closer evaluation, particularly in the context of sex, is the infrapatellar fat pad (IFP). We previously demonstrated that removal of the IFP had short-term beneficial effects for a cohort of male Dunkin-Hartley guinea pigs. The present project was designed to elucidate the influence of IFP removal in females of this OA-prone strain. It was hypothesized that resection of the IFP would reduce the development of OA in knees of a rodent model predisposed to the disease. Methods: Female guinea pigs (n=16) were acquired at an age of 2.5 months. Surgical removal of the IFP and associated synovium complex (IFP/SC) was executed at 3 months of age. One knee had the IFP/SC resected; a comparable sham surgery was performed on the contralateral knee. All animals were subjected to voluntary enclosure monitoring and dynamic weight-bearing, as well as compulsory treadmill-based gait analysis monthly; baseline data was collected prior to surgery. Guinea pigs were euthanized at 7 months. Knees from eight animals were evaluated via histology, mRNA expression, and immunohistochemistry (IHC); knees from the remaining eight animals were allocated to microcomputed tomography (microCT), biomechanical analyses (whole joint testing and indentation relaxation testing), and atomic absorption spectroscopy (AAS). Results: Fibrous connective tissue (FCT) replaced the IFP/SC. Mobility/gait data indicated that unilateral IFP/SC removal did not affect bilateral hindlimb movement. MicroCT demonstrated that osteophytes were not a significant feature of OA in this sex; however, trabecular thickness (TbTh) in medial femorae decreased in knees containing the FCT. Histopathology scores were predominantly influenced by changes in the lateral tibia, which demonstrated that histologic signs of OA were increased in knees containing the native IFP/SC versus those with the FCT. Similarly, indentation testing demonstrated higher instantaneous and equilibrium moduli in the lateral tibial articular cartilage of control knees with native IFPs. AAS of multiple tissue types associated with the knee revealed that zinc was the major trace element influenced by removal of the IFP/SC. Conclusions: Our data suggest that the IFP/SC is a significant component driving knee OA in female guinea pigs and that resection of this tissue prior to disease has short-term benefits. Specifically, the formation of the FCT in place of the native tissue resulted in decreased cartilage-related OA changes, as demonstrated by reduced Osteoarthritis Research Society International (OARSI) histology scores, as well as changes in transcript, protein, and cartilage indentation analyses. Importantly, this model provides evidence that sex needs to be considered when investigating responses and associated mechanisms seen with this intervention.

The thickness change ratio and preservation ratio of the infrapatellar fat pad are related to anterior knee pain in patients following medial patellofemoral ligament reconstruction.

BACKGROUND: The infrapatellar fat pad (IPFP) lies extrasynovial and intracapsular, preserving the joint cavity and serving as a biochemical regulator of inflammatory reactions. However, there is a lack of research on the relationship between anterior knee pain (AKP) and the IPFP after medial patellofemoral ligament reconstruction (MPFLR). Pinpointing the source of pain enables clinicians to promptly manage and intervene, facilitating personalized rehabilitation and improving patient prognosis. METHODS: A total of 181 patients were included in the study. These patients were divided into the AKP group (n = 37) and the control group (n = 144). Clinical outcomes included three pain-related scores, Tegner activity score, patient satisfaction, etc. Imaging outcomes included the IPFP thickness, IPFP fibrosis, and the IPFP thickness change and preservation ratio. Multivariate analysis was used to determine the independent factors associated with AKP. Finally, the correlation between independent factors and three pain-related scores was analyzed to verify the results. RESULTS: The control group had better postoperative pain-related scores and Tegner activity score than the AKP group (P < 0.01). The AKP group had lower IPFP thickness change ratio and preservation ratio (P < 0.001), and smaller IPFP thickness (P < 0.05). The multivariate analysis revealed that the IPFP thickness change ratio [OR = 0.895, P < 0.001] and the IPFP preservation ratio [OR = 0.389, P < 0.001] were independent factors related to AKP, with a significant correlation between these factors and pain-related scores [|r| > 0.50, P < 0.01]. CONCLUSIONS: This study showed the lower IPFP change ratio and preservation ratio may be independent factors associated with AKP after MPFLR. Early detection and targeted intervention of the underlying pain sources can pave the way for tailored rehabilitation programs and improved surgical outcomes. LEVEL OF EVIDENCE LEVEL III.

Unveiling rarity: Myoepithelioma in the minor salivary gland of buccal mucosa - A case report.

INTRODUCTION: Tumours of salivary glands are rare and have various histo-pathological subtypes. Myoepitheliomas were first classified by Sheldon et al. and the criterion to classify or diagnose it was first defined by Barnes et al. and Sciubba and Brannon. Myoepithelioma accounts for less than 1 % of all salivary gland tumours, 40 % of these tumours occur in the parotid gland while 21 % occur in the minor salivary glands. A case of myoepithelioma of a minor salivary gland of the cheek is described, emphasizing the problems of the differential diagnosis. PRESENTATION OF THE CASE: A 40-year-old female reported to the department with a complaint of a cheek bite on her right side for a few months. The physical examination showed a presence of lobulated whitish mucosa on the right buccal mucosa at the level of the occlusal plane, on palpation it revealed a non-painful mass approximately 1.5 cm in radius, mobile to bimanual palpation. An excisional biopsy was performed under local anaesthesia. Microscopic and immunohistochemistry confirmed the tumour to be a myoepithelioma of a minor salivary gland with the absence of definitive features of malignancy. DISCUSSION: Due to their infrequency and multiplicity of histopathology, myoepitheliomas present difficulties in diagnosis. Cellular varieties can be misdiagnosed as malignancies. A key to determining diagnostic criteria for myoepitheliomas is to study cellular morphology, cytoplasmic filament expression, and ultrastructural features of the tumour and apply this information to defining myoepitheliomas. CONCLUSION: Myoepitheliomas are rare tumours, utilization of immunohistochemical staining and electron microscopy are useful tools for the diagnosis of myoepitheliomas to ensure proper treatment and follow-up.

Role of joint adipose tissues in osteoarthritis.

Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention focused on the role of adipose tissues (AT). In addition to the involvement of visceral and subcutaneous AT via systemic ways, many arguments also highlight the involvement of local AT, present in joint tissues. Local AT include intra-articular AT (IAAT), which border the synovium, and bone marrow AT (BMAT) localized within marrow cavities in the bones. This review describes the known features and involvement of IAAT and BMAT in joint homeostasis and OA. Recent findings evidence that alteration in magnetic resonance imaging signal intensity of infrapatellar fat pad can be predictive of the development and progression of knee OA. IAAT and synovium are partners of the same functional unit; IAAT playing an early and pivotal role in synovial inflammation and fibrosis and OA pain. BMAT, whose functions have only recently begun to be studied, is in close functional interaction with its microenvironment. The volume and molecular profile of BMAT change according to the pathophysiological context, enabling fine regulation of haematopoiesis and bone metabolism. Although its role in OA has not yet been studied, the localization of BMAT, its functions and the importance of the bone remodelling processes that occur in OA argue in favour of a role for BMAT in OA.

Association between quadriceps fat pad edema and patellofemoral osteoarthritis: a quantitative Q-Dixon-based magnetic resonance imaging (MRI) analysis.

Background: Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon. Methods: This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA. Results: Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*). Conclusions: QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.

Sonographic Characterization of the Pericruciate Fat Pad with the Use of Compression Elastography-A Cross-Sectional Study among Healthy and Post-Injured Patients.

Background: The pericruciate fat pad (PCFP) in the knee joint is still insufficiently studied despite its potential role in knee pathologies. This is the first reported study which aimed to clarify the characteristics of the PCFP in healthy individuals and contrast them with cases of post-traumatic injuries. Methods: Conducted as a retrospective cross-sectional study (n = 110 knees each) following STROBE guidelines, it employed grayscale ultrasound with echogenicity measurement, compression elastography with elasticity measurement, and Color Doppler for blood flow assessment. Results: PCFP showed a homogenic and hyperechoic echostructure. The echogenicity of the PCFP was higher than that of the posterior cruciate ligament (PCL) (p < 0.001, z-score = 8.97) and of the medial head of gastrocnemius (MHG) (p = 0.007, z-score = 2.72) in healthy knees, but lower than subcutaneous fat (SCF) (p < 0.001, z-score = -6.52). Post-injury/surgery, PCFP echogenicity surpassed other structures (p < 0.001; z-score for PCL 12.2; for MHG 11.65 and for SCF 12.36) and notably exceeded the control group (p < 0.001, z-score = 8.78). PCFP elasticity was lower than MHG and SCF in both groups, with significantly reduced elasticity in post-traumatic knees (ratio SCF/PCFP 15.52 ± 17.87 in case group vs. 2.26 ± 2.4 in control group; p < 0.001; z-score = 9.65). Blood flow was detected in 71% of healthy PCFPs with three main patterns. Conclusions: The main findings, indicating increased echogenicity and reduced elasticity of PCFP post-trauma, potentially related to fat pad fibrosis, suggest potential applications of echogenicity and elasticity measurements in detecting and monitoring diverse knee pathologies. The description of vascularity variations supplying the PCFP adds additional value to the study by emphasizing the clinically important role of PCFP as a bridge for the middle genicular artery on its way to the inside of the knee joint.

Correction of severe upper-eyelid sunken deformity in Asians by double-eyelid procedure and combination of orbital fat pad repositioning and autologous fat transplantation: a one-year follow-up study of 79 cases.

Background: Nowadays, people's pace of life continues to rapid up, and many bad habits will accelerate the aging of the eye periphery, and patients with sunken upper eyelids are to be found in younger people. In young Asians, single eyelids are often accompanied by upper eyelid depression, so correcting the upper eyelid depression during blepharoplasty becomes a higher challenge for plastic surgeons. Current surgical methods for upper eyelid depression include three major categories: tissue repositioning, injection and filling, and combined use. According to grades 1 and 2 are mild or moderate upper eyelid sunken. The sunken can be well corrected only by repositioning the orbital fat pad, while the correction effect for severe upper eyelid sunken in grades 3 and 4 is Poor, need to be used in combination to achieve the desired effect. Purpose: The authors sought to determine whether, for patients with single eyelids and severe upper eyelid depression of grades 3 and 4, combined with orbital fat pad repositioning and autologous fat transplantation during blepharoplasty, an aesthetic and youthful blepharoplasty can be achieved. Methods: This study included 79 patients with single eyelids and severe upper eyelid depression of grades 3 and 4 who received treatment between June 2020 and July 2022. All patients underwent double eyelid surgery plus orbital fat repositioning and autologous fat grafting. Results: After a minimum follow-up period of 1 year, overall patient satisfaction was 92%. The recurrence rate within the first year was 6% and the complication rate was 5%. Conclusion: This combined surgery may be an option for young Asians with single eyelids and severe upper eyelid depression. In this study, the surgery resulted in natural-looking double eyelids and younger-looking eye sockets in most patients. A combination of different surgical methods based on the patient's preoperative condition is critical to achieving long-term correction.

Morphological Evaluation and Immunohistochemical Analysis of the Reparative Potential of the Buccal Fat Pad.

Background and Objectives: There are many surgical techniques for oroantral communication treatment, one of which is the buccal fat pad. Of particular interest is the high reparative potential of the buccal fat pad, which may be contributed to by the presence of mesenchymal stem cells. The purpose of this work is to evaluate the reparative potential of BFP cells using morphological and immunohistochemical examination. Materials and Methods: 30 BFP samples were provided by the Clinic of Maxillofacial and Plastic Surgery of the Russian University of Medicine (Moscow, Russia) from 28 patients. Morphological examination of 30 BFP samples was performed at the Institute of Clinical Morphology and Digital Pathology of Sechenov University. Hematoxylin-eosin, Masson trichrome staining and immunohistochemical examination were performed to detect MSCs using primary antibodies CD133, CD44 and CD10. Results: During staining with hematoxylin-eosin and Masson's trichrome, we detected adipocytes of white adipose tissue united into lobules separated by connective tissue layers, a large number of vessels of different calibers, as well as the general capsule of BFP. The thin connective tissue layers contained neurovascular bundles. Statistical processing of the results of the IHC examination of the samples using the Mann-Whitney criterion revealed that the total number of samples in which the expression of CD44, CD10 and CD133 antigens was confirmed was statistically significantly higher than the number of samples where the expression was not detected (p < 0.05). Conclusions: During the morphological study of the BFP samples, we revealed statistically significant signs of MSCs presence (p < 0.05), including in the brown fat tissue, which proves the high reparative potential of this type of tissue and can make the BFP a choice option among other autogenous donor materials when eliminating OAC and other surgical interventions in the maxillofacial region.

Evaluation of abdominal fat pad aspiration highlighting challenges to interpretation.

INTRODUCTION: Fine-needle aspiration (FNA) of abdominal fibroadipose tissue is a commonly utilized method for the detection of amyloidosis. While generally regarded as an accurate and specific detection method, the sensitivity is variable. The objective of this study was to investigate the performance of fat pad FNAs in detecting amyloidosis relative to other tissue biopsies. MATERIALS AND METHODS: Fat pad FNA results from January 1, 2014, to December 31, 2022, were catalogued. Clinical data including FNA indication were ascertained for each case. The results of any subsequent tissue biopsy/biopsies evaluated for amyloidosis by Congo red staining were also assessed. Challenges to diagnostic interpretation were explored. RESULTS: A total of 334 fat pad FNAs were identified. The most common indications were peripheral neuropathy (29.3%), cardiomyopathy/heart failure (28.1%), monoclonal gammopathy (27.8%), and multiple myeloma/lymphoplasmacytic lymphoma (21.0%). Cytologic interpretations were: 7 (2.1%) nondiagnostic, 284 (85.0%) negative, 18 (5.4%) indeterminate, 16 (4.8%) suspicious, and 9 (2.7%) positive for amyloid deposition. In our sample, 103 (30.8%) patients had Congo red testing performed on a subsequent surgical specimen(s) including: 3 of 7 of nondiagnostic cases, none which were positive on the subsequent surgical; 70 of 284 negative cases, 27 which were positive on the subsequent surgical; 11 of 18 indeterminate cases, 7 which were positive on the subsequent surgical; 13 of 16 suspicious cases, 2 which were positive on the subsequent surgical; and 6 of 9 positive cases, 3 which were positive on the subsequent surgical. Challenges to FNA interpretation included scant cellularity, focal staining/birefringence, and overstaining. CONCLUSIONS: It is best to view fat pad aspiration versus other tissue biopsy results as complimentary diagnostic tests that should be interpreted in the context of the clinical setting and overall clinical suspicion for amyloidosis.

Effect of preservation of Hoffa's fat pad on patellar height in primary total knee arthroplasty procedures.

BACKGROUND: We have previously reported our experience of the effect of complete excision of Hoffa's fat pad on patella height post TKR. In this study, we compared the change of patellar height post TKR before and after the senior author changed his practice to preserving Hoffa's fat pad. METHODS: This was a retrospective analysis of a prospective series of TKRs performed or directly supervised by the senior author. In Group 1 were 72 patients performed before April 2011 who had complete excision of Hoffa's fat pad to maximise exposure during the procedure. In Group 2 were 138 patients performed after April 2011 who had the minimum excision of Hoffa's fat pad to allow adequate surgical exposure. The surgical technique and rehabilitation protocol were identical in all other respects. Patellar height was assessed using the Caton-Deschamps Index both immediately postoperative and at a minimum follow up of 1 year. RESULTS: Group 1 included 28 males, 44 females with mean age 68.36 years. The mean CDI in this group changed from 0.54 immediately post-operatively to 0.46 at minimum one year follow-up (P = 0.001) indicating progressive patella baja. Group 2 included 56 males, 82 females with mean age 65 years. The mean CDI changed from 0.67 immediately post-operative to 0.68 at minimum one year post follow-up (P = 0.32) indicating no statistically or clinically relevant post-operative change in patellar height. CONCLUSION: Total excision of Hoffa's fat pad is associated with progressive post-operative patella baja. This can be avoided by resecting the minimum amount of fat pad to allow adequate exposure during the procedure.

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.

Culture of Hoffa fat pad mesenchymal stem/stromal cells on microcarrier suspension in vertical wheel bioreactor for extracellular vesicle production.

BACKGROUND: Mesenchymal stromal cells (MSCs) are increasingly employed in regenerative medicine approaches for their immunomodulatory and anti-inflammatory properties, which are encoded in their secretome including extracellular vesicles (EVs). The Hoffa fat pad (HFP) located infrapatellarly harbours MSCs that could assist in tissue homeostasis in osteoarthritic joints. Intraarticular injection therapies based on blood products could modulate the populations of released HFP-MSC-EVs in a quantitative manner. METHODS: To obtain amounts of HFP-MSC-derived EVs that allow pre-clinical evaluation, suitable EV production systems need to be developed. This work investigates the release of EVs from primary HFP-MSCs cultivated in a 3D environment using microcarrier suspension culture in a vertical wheel bioreactor in comparison to conventional 2D culture. To simulate an intraarticular blood product therapy, cultures were treated with citrate-anticoagulated platelet-rich plasma (CPRP) or hyperacute serum (hypACT) before EV collection. HFP-MSC-EVs are enriched via ultrafiltration and characterised via Western Blot, nanoparticle tracking analysis in scatter as well as fluorescence mode. EV potency was determined via RT-qPCR analysing the expression of type II and X collagen (COL2 and COL10), as well as inducible nitric oxide synthase (iNOS) in primary OA chondrocytes. RESULTS: Blood product supplementation elevated HFP-MSC metabolic activity as determined via XTT assay over the course of 14 days. 3D culture resulted in a roughly 100-fold EV yield compared to 2D culture and elevated number of EVs released per cell. Total protein content correlated with the EV concentration. While typical EV marker proteins such as CD9, CD63 or Alix were detected in total protein extracts, CD9 and CD73 colocalised on individual EVs highlighting their cell origin. The type of blood product treatment did not affect the size or concentration of EVs obtained from HFP-MSCs. Assessing potency of 3D culture EVs in comparison to 2D EVs revealed superior biological activity with regard to inhibition of inflammation, inhibition of chondrocyte hypertrophy and induction of cartilage-specific ECM production. CONCLUSIONS: HFP-MSCs proliferate in presence of human blood products indicating that animal serum in culture media can be avoided in the future. The culture of HFP-MSCs in the employed bioreactor was successfully used to generate quantities of EVs that could allow evaluation of HFP-MSC-EV-mediated effects in pre-clinical settings. In addition, EV potency of 3D EVs is superior to EVs obtained in conventional 2D culture flasks.

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.

Modification of Mesenchymal Stem/Stromal Cell-Derived Small Extracellular Vesicles by Calcitonin Gene Related Peptide (CGRP) Antagonist: Potential Implications for Inflammation and Pain Reversal.

During the progression of knee osteoarthritis (OA), the synovium and infrapatellar fat pad (IFP) can serve as source for Substance P (SP) and calcitonin gene-related peptide (CGRP), two important pain-transmitting, immune, and inflammation modulating neuropeptides. Our previous studies showed that infrapatellar fat pad-derived mesenchymal stem/stromal cells (MSC) acquire a potent immunomodulatory phenotype and actively degrade Substance P via CD10 both in vitro and in vivo. On this basis, our hypothesis is that CD10-bound IFP-MSC sEVs can be engineered to target CGRP while retaining their anti-inflammatory phenotype. Herein, human IFP-MSC cultures were transduced with an adeno-associated virus (AAV) vector carrying a GFP-labelled gene for a CGRP antagonist peptide (aCGRP). The GFP positive aCGRP IFP-MSC were isolated and their sEVs' miRNA and protein cargos were assessed using multiplex methods. Our results showed that purified aCGRP IFP-MSC cultures yielded sEVs with cargo of 147 distinct MSC-related miRNAs. Reactome analysis of miRNAs detected in these sEVs revealed strong involvement in the regulation of target genes involved in pathways that control pain, inflammation and cartilage homeostasis. Protein array of the sEVs cargo demonstrated high presence of key immunomodulatory and reparative proteins. Stimulated macrophages exposed to aCGRP IFP-MSC sEVs demonstrated a switch towards an alternate M2 status. Also, stimulated cortical neurons exposed to aCGRP IFP-MSC sEVs modulate their molecular pain signaling profile. Collectively, our data suggest that yielded sEVs can putatively target CGRP in vivo, while containing potent anti-inflammatory and analgesic cargo, suggesting the promise for novel sEVs-based therapeutic approaches to diseases such as OA.

Synovium and infrapatellar fat pad share common mesenchymal progenitors and undergo coordinated changes in osteoarthritis.

Osteoarthritis (OA) affects multiple tissues in the knee joint, including the synovium and intra-articular adipose tissue (IAAT) that are attached to each other. However, whether these two tissues share the same progenitor cells and hence function as a single unit in joint homeostasis and diseases is largely unknown. Single-cell transcriptomic profiling of synovium and infrapatellar fat pad (IFP), the largest IAAT, from control and OA mice revealed five mesenchymal clusters and predicted mesenchymal progenitor cells (MPCs) as the common progenitors for other cells: synovial lining fibroblasts (SLFs), myofibroblasts (MFs), and preadipocytes 1 and 2. Histologic examination of joints in reporter mice having Dpp4-CreER and Prg4-CreER that label MPCs and SLFs, respectively, demonstrated that Dpp4+ MPCs reside in the synovial sublining layer and give rise to Prg4+ SLFs and Perilipin+ adipocytes during growth and OA progression. After OA injury, both MPCs and SLFs gave rise to MFs, which remained in the thickened synovium at later stages of OA. In culture, Dpp4+ MPCs possessed mesenchymal progenitor properties, such as proliferation and multilineage differentiation. In contrast, Prg4+ SLFs did not contribute to adipocytes in IFP and Prg4+ cells barely grew in vitro. Taken together, we demonstrate that the synovium and joint fat pad are one integrated functional tissue sharing common mesenchymal progenitors and undergoing coordinated changes during OA progression.

Both synovium and intra-articular adipose tissue (IAAT) in knee joint play a critical role in joint health and osteoarthritis (OA) progression. Recent single-cell RNA-sequencing studies have been performed on the mouse and human synovium. However, IAATs residing in close proximity to the synovium have not been studied yet. Our study reveals mesenchymal cell heterogeneity of synovium/infrapatellar fat pad (Syn/IFP) tissue and their OA responses. We identify Dpp4+ multipotent progenitors as a source that give rise to Prg4+ lining layer fibroblasts in the synovium, adipocytes in the IFP, and myofibroblasts in the OA Syn/IFP tissue. Our work demonstrates that Syn/IFP is a functionally connected tissue that shares common mesenchymal progenitors and undergoes coordinated OA changes. This novel insight advances our knowledge of previously understudied joint tissues and provides new directions for drug discovery to treat joint disorders.