The February 2025 Knee Roundup³⁶⁰ looks at: Once-weekly semaglutide in patients with obesity and knee osteoarthritis; How many patients should have a unicompartmental knee arthroplasty?; Staged revision of the infected knee arthroplasty and endoprosthesis; The metal allergy argument and knee arthroplasty; Is kinematic alignment all it’s cracked up to be?; Is bone-patella-bone the gold standard for revision?; Blood flow restriction and the dissatisfied knee arthroplasty.

Aims. Approximately 10% to 20% of knee arthroplasty patients are not satisfied with the result, while a clear indication for revision surgery might not be present. Therapeutic options for these patients, who often lack adequate quadriceps strength, are limited. Therefore, the primary aim of this study was to evaluate the clinical effect of a novel rehabilitation protocol that combines low-load resistance training (LL-RT) with blood flow restriction (BFR). Methods. Between May 2022 and March 2024, we enrolled 45 dissatisfied knee arthroplasty patients who lacked any clear indication for revision to this prospective cohort study. All patients were at least six months post-surgery and had undergone conventional physiotherapy previously. The patients participated in a supervised LL-RT combined with BFR in 18 sessions. Primary assessments included the following patient-reported outcome measures (PROMs): Knee injury and Osteoarthritis Outcome Score (KOOS); Knee Society Score: satisfaction (KSSs); the EuroQol five-dimension five-level questionnaire (EQ-5D-5L); and the pain catastrophizing scale (PCS). Functionality was assessed using the six-minute walk Test (6MWT) and the 30-second chair stand test (30CST). Follow-up timepoints were at baseline, six weeks, three months, and six months after the start. Results. Six weeks of BFR with LL-RT improved all the PROMs except the sports subscale of the KOOS compared to baseline. Highest improvements after six weeks were found for quality of life (QoL) (mean 28.2 (SD 17.2) vs 19 (SD 14.7); p = 0.002), activities of daily living (mean 54.7 (SD 18.7) vs 42.9 (SD 17.3); p < 0.001), and KSSs (mean 17.1 (SD 8.8) vs 12.8 (SD 6.7); p < 0.001). PROMs improvements continued to be present at three-month and six-month follow-up compared to baseline. However, no significant differences were observed in the paired comparisons of the six-week, three-month, and six-month follow-up. The same trends are observed for the 6MWT and 30CST. Conclusion. The reported regime demonstrates improved QoL and function of dissatisfied knee arthroplasty patients. In light of this, the pathway described may provide a valuable and safe treatment option for dissatisfied knee arthroplasty patients for whom therapeutic options are limited. Cite this article: Bone Joint J 2024;106-B(12):1416–1425

Introduction. Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). Interestingly, content and dose of exercise interventions seem to be important for the effect of exercise interventions, but the optimal content and dose is unknown. This warrants randomized controlled trials providing evidence for the optimal exercise program in Hip OA. The aim of this trial was to investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance, hip pain and hip-related quality of life in patients with hip OA. Method. This was a multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. 160 participants with clinically diagnosed hip OA were recruited from hospitals and physiotherapy clinics and randomly assigned to twelve weeks of PRT or NEMEX. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS). Result. The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, 0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX. For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX. Conclusion. In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL

Introduction. Humans Functions (locomotion, protection of organs, reproduction) require a strong support system (bones). The ‘Osteostasis’ is the ability of maintaining the bone structure, its mechanical characteristics and function. Five principles are required for an efficient bone system:. Basic Requirements:. 1) Stability and 2) Function. Repair System (like house building in desert or sea):. 3) Roads (vessels), 4) Materials (calories, proteins), 5) Workers (bone cells). Analysis of bone problems through these principles bring to optimised treatments. Materials & Methods. Measurements (>700 lengthening, 32-year follow-up, Full WB Albizzia/G-Nails FWBAG): Bone-DEXA, WB conditions, muscle, fat, etc. Principle-1. Solid bone replacement with a 100% biocompatible and reliable FWBAG with sports (POD0). Principle-2. Bone, Muscle & neural integrity for function Principle-3. Vascular flow lesions induce non-healing (arteriography). Muscle activity accounts for 90% of bone blood flow, ×10 by sports. Required: Checks (arteriography) and treatments (training). Principle-4. Food (NRV Kcal × 2–3, 20–25% proteins). Principle-5. Maintain bone cells and increase them. Suppress ‘opening’, ‘venting’, ‘drainages’. Results. Principle1. Nail fracture (1.2%), nail dysfunction (0%) with FWBAG. Principle2. Intensive sports preop and from POD0 - Principle3. Increased preop vascular supply & muscle force, postop resistance sports fasten recovery. Wheel-chair or low activity decreases healing. Principle4. 6–9 cm circumference loss (non WB-nails or no proper training); 0 cm circumference loss (gain <10 cm) with intense resistance training + high calory intake. - Principle5. Bone cells preservation (no opening, IM saw, increasing bone cells) allow Healing Index down to 8D/cm. Conclusions. The ‘5P’ allow reaching treatment targets by optimisation of problem solving, maintaining Osteostasis. What would I like or tolerate for me? How can I reach it? Full WB and sports from POD0 was a target 38 years-ago, still not enforced by most of us. Resistance sports, high-calory intake suppress muscle loss and fasten healing, thanks to muscle blood flow and the ‘5P’

Introduction. A 6cm femoral gain requires 5-Y during normal growth, but only 6–8-W surgically (x30–40 faster). In lengthening surgery, losses of muscle force (MF) and circumferences (MC) are major. Recovery is long, preventing sports till bone fusion. Can we maintain MC and strength throughout the entire lengthening and how?. We monitored for over 30 years patients for muscle force (isokinetic), circumferences, activities (including sports) and food intake, and acted on the 5 principles of the Osteostasis. Materials & Methods. Over 750 femoral lengthening with Full WB Nails (FWBN) got Isokinetic testing (≧1991), circumferences measurements (≧2012; 20-15-10-5-0cm above patella, max-calf, mini/max-ankle), food intake (≧2012), using MyFitnessPal App (≧2016), gradually enforced. Preoperative training along with a daily post-operative training are supervised by our trainers. Recommendations for food intake and activities were provided. Patients noted on a specific App all parameters. Compliance was noted. Results. Instead of a traditional 7–9cm circumference loss for 8–10cm gains using Ex-fix or nails, with FWBN and our protocols, no MC loss could be noted in compliant pre-trained patients, intensive early post-op resistance training, high calory intake (M:>4200, F:>3000; 20–25% Proteins) and supplements (no fat pad increase). Bone fusion could be obtained at the end of lengthening or within short weeks (Healing Index down to 8D/cm). Non-compliant patients (or using morphine), lost weight and MC. Conclusions. Increasing by 8–10cm muscle length, even bilaterally, and maintaining MC during lengthening, is possible, with very fast bone fusion. It requires building up several hundred of grams of muscles. The ‘building up equation’ associating resistance bike from the early post-operative phase with sports, strong food intake with increased protein intake, and added supplements with no morphine medication, proved to boost circumferences and bone fusion. It induced fast recovery, walking and sports capacities

7–20 % of the patients with a total knee arthroplasty (TKA) are dissatisfied without an indication for revision. Therapeutic options for this patient population with mostly a lack of quadriceps strength are limited. The purpose of this study is to evaluate the effect of six weeks low load resistance training with blood flow restriction (BFR) on the clinical outcome in these unhappy TKA patients. Thirty-one unhappy TKA patients (of the scheduled fifty patients) without mechanical failure were included in this prospective study since 2022. The patients participate in a supervised resistance training combined with BFR, two times a week during nine weeks. Patients were evaluated by the Knee Osteoarthritis Outcome Score (KOOS), Knee Society Score: satisfaction (KSSs) and the Pain Catastrophizing Scale (PCS). Functionality was tested using the Six Minute Walk Test (6MWT) and the 30-Second Chair Stand Test (30CST). Follow-up took place at six weeks, three months and six months after the start. Six weeks training with BFR provided statistically significant improvements in all the KOOS subscales compared to the baseline, especially for symptoms (55.1 (±15.4) versus 48.0 (±16.5); p<0.001), activities in daily living (50.3 (±21.1) versus 43.7 (±17.2); p<0.00) and quality of life (24.6 (±18.5) versus 17.3 (±13.0); p<0.001). The PCS reduced from 27.4 (±11.0) to 23.2 (±11.4) at six weeks (p<0.01), whereas the KSSs increased from 11.8 (±6.5) to 14.9 (±7.6) (p=0.021). Both the 6MWT and the 30CST improved statistically significant from respectively 319.7 (±15.0) to 341.6m (±106.5) (p<0.01) and 8.6 (±3.9) to 9.3 times (±4.5) (p<0.01). Blood flow restriction appears to enhance the quality of life and functional performance of unhappy TKA patients. Based on these preliminary results, BFR seems to be a promising and valuable alternative for these TKA patients with limited therapeutic options

As high incidences of tendinopathies are observed particularly in those who intensively use their tendons, we assume that pathological changes are caused, at least partially, by mechanical overload. This has led to the so-called overload hypothesis, explaining the development of tendinopathies by structural failure resulting from excessive load. At the same time, tendon loading is an important part in tendon rehabilitation. Currently, exercise treatment approaches such as eccentric training or heavy load resistance training are widely applied in tendinopathy rehabilitation, with good clinical results such as an improvement in function and a reduction in pain. Particularly those rehabilitative approaches which impose high strains on the tendon may induce an adaptation of the tendon's mechanical properties such as increased tendon stiffness. An increased tendon stiffness is often interpreted as desirable, as it may protect the tendon from overloading and thus prevent future strain injuries. However, the tendinopathic tendon is not necessarily less stiff than the tendon in the contralateral leg and an improvement in tendon stiffness is not necessarily accompanied by an improvement in tendon pain or function. In addition, metabolic factors, resulting e.g. in low-level systemic inflammation, may contribute to pathological tendon tissue changes and are not necessarily affected by an exercise program, while nutritional interventions or dietary supplements may potentially affect tendon cell metabolism. Indeed, dietary supplements have been introduced as an additional therapeutic approach in the treatment of tendinopathies in recent years, and their positive curative effects have been reported for both the general population and athletes. In the management of tendinopathies, it may thus be advisable if therapeutic approaches aim to address both tendon mechanics and tendon metabolism for better treatment effectiveness and a sustainable improvement in pain and function

Aims. The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach. Methods. A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous. Results. Of 27 questions and statements on patellar instability, three achieved unanimous consensus, 14 achieved strong consensus, five achieved consensus, and five did not achieve consensus. Conclusion. The statements that reached unanimous consensus were that an assessment of physeal status is critical for paediatric patients with patellar instability. There was also unanimous consensus on early mobilization and resistance training following nonoperative management once there is no apprehension. The statements that did not achieve consensus were on the importance of immobilization of the knee, the use of orthobiologics in nonoperative management, the indications for MPFC repair, and whether a vastus medialis oblique advancement should be performed. Cite this article: Bone Joint J 2023;105-B(12):1259–1264

Aims

Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR).

Aims

The aim of this study was to determine the effectiveness of home-based prehabilitation on pre- and postoperative outcomes in participants awaiting total knee (TKA) and hip arthroplasty (THA).

The December 2022 Research Roundup. 360. looks at: Halicin is effective against Staphylococcus aureus biofilms in vitro; Synovial fluid and serum neutrophil-to-lymphocyte ratio: useful in septic arthritis?; Transcutaneous oximetry and wound healing; Orthopaedic surgery causes gut microbiome dysbiosis and intestinal barrier dysfunction; Mortality in alcohol-related cirrhosis: a nationwide population-based cohort study; Self-reported resistance training is associated with better bone microarchitecture in vegan people

The December 2022 Shoulder & Elbow Roundup. 360. looks at: Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears; Resistance training combined with corticosteroid injections or tendon needling in patients with lateral elbow tendinopathy; Two-year functional outcomes of completely displaced midshaft clavicle fractures in adolescents; Patients who undergo rotator cuff repair can safely return to driving at two weeks postoperatively; Are two plates better than one? A systematic review of dual plating for acute midshaft clavicle fractures; Treatment of acute distal biceps tendon ruptures; Rotator cuff tendinopathy: disability associated with depression rather than pathology severity; Coonrad-Morrey total elbow arthroplasty implications in young patients with post-traumatic sequelae

Aims. The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model. Methods. We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics. Results. After the bioinformatic analysis, the PI3K-Akt signalling pathway and the regulation of actin cytoskeleton in particular were highlighted among the top ten pathways with the most differentially expressed genes involved in the young/MID and MID+ T/MID groups. The expression of Gng5, Atf2, and Rtor in the PI3K-Akt signalling pathway was higher in the young and MID+ T groups compared with the MID group. Similarly, Limk1, Arhgef12, and Araf in the regulation of the actin cytoskeleton pathway had a similar bias. Moreover, the protein expression profiles of Atf2, Rptor, and Ccnd3 in each group were paralleled with the results of NGS. Conclusion. Our results revealed that age-induced muscle loss might result from age-influenced genes that contribute to muscle development in SCs. After resistance training, age-impaired genes were reactivated, and age-induced genes were depressed. The change fold in these genes in the young/MID mice resembled those in the MID + T/MID group, suggesting that resistance training can rejuvenate the self-renewing ability of SCs by recovering age-influenced genes to prevent sarcopenia. Cite this article: Bone Joint Res 2022;11(2):121–133

Introduction and Objective. Hip osteoarthritis (OA) is the leading cause for total hip arthroplasty (THA). Although, being considered as the surgery of the century up to 23% of the patients report long-term pain and deficits in physical function and muscle strength may persist after THA. Progressive resistance training (PRT) appear to improve several outcomes moderately in patients with hip OA. Current treatment selection is based on low-level evidence as no randomised controlled trials have compared THA to non-surgical treatment. The primary objective of this trial is to determine the effectiveness of THA followed by standard care compared to 12 weeks of supervised PRT followed by 12 weeks of optional unsupervised PRT, on changes in hip pain and function, in patients with severe hip OA after 6 months. Materials and Methods. This is a protocol for a multicentre, parallel-group, assessor blinded, randomised controlled superiority trial. Patients aged ≥50 years with clinical and radiographic hip OA found eligible for THA by an orthopaedic surgeon will be randomised to THA or PRT (allocation 1:1). The primary outcome will be change in patient-reported hip pain and function, measured using the Oxford Hip Score. Key secondary outcomes will be change in the Hip disability and Osteoarthritis Outcome Score subscales, University of California Los Angeles Activity Score, 40-meter fast-paced walk test, 30-second chair stand test, and number of serious adverse events. Results. The trial has been approved by The Regional Committees on Health Research Ethics for Southern Denmark (Project-ID: S-20180158) in February 2019 and registration was performed at . ClinicalTrials.gov. (NCT04070027) in August 2019. Recruitment was initiated on the 2. nd. of September 2019 and the final deadline will be on the 30. th. of June 2021, or when a sample size of 120 patients has been accomplished. Conclusions. The results of the current trial are expected to enable evidence-based recommendations, which may be used to facilitate the shared-decision making process in the discussion of treatment strategy for the individual patient with severe hip OA. All results will be presented in peer-reviewed scientific journals and international conferences

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data.

Cite this article: Bone Joint Res 2020;9(11):798–807.

Patient perceptions regarding the functional outcomes and return to sports after shoulder replacement are often pessimistic, with many patients presenting for shoulder replacement surgery after months or years of avoiding the procedure so they could continue to live the current life they have, despite the increasing pain and dysfunction. Less common, but becoming more frequent, patients present with expectations that they will be able to return to all activities including heavy resistance training, cross-fit, rock climbing, and other strenuous overhead sports. In the past, little information has been available regarding the activities of shoulder arthroplasty patients after surgery. Typically, the boundaries have been set by the surgeon, with many patients cautioned or even prohibited from overhead sports, weight training, or heavy work responsibilities. A typical set of guidelines may include no repetitive overhead sports, except for recreational swimming, and no lifting over 20 pounds. Golf, jogging, hiking and other activities are allowed. The origin of these restricted guidelines and expectations is unknown, but many believe that since the results of shoulder replacements are less favorable in younger patients, it may be due to the overuse or abuse of the shoulder joint that is more typical at a younger age. Others have suggested that common sense prevails and that an artificial joint made of metal and plastic has a finite number of total movements and tolerance to resistance activities, and therefore keeping these activities at a minimum would extend the longevity of the artificial joint. None of these concepts are backed up by evidence-based literature, essentially reflecting the personal bias of the surgeons who care for patients with these problems. Despite all of the sophisticated research, scoring scales, outcome measures, and value-based metrics, the only outcome that really matters is whether the patient can return back to their normal way of life, at home, at work, during sport, or any activity that is important to them. Recent studies of patients who have had joint replacement surgery have revealed that our patients who participated in sports and work activities before surgery have a strong predilection to returning to those activities after successful shoulder replacement. The most common sports that shoulder arthroplasty patients enjoy including golf, swimming, tennis, but may also include many other choices including fitness activities, rowing, skiing, basketball, and softball. As expected, the return to these sports is less for reverse shoulder arthroplasty patients vs. anatomic shoulder arthroplasty patients. In a systematic review, more than 90% of anatomic shoulder replacement patients returned to sport, while 75% of reverse shoulder arthroplasty patients returned to some sporting activity. This may reflect the constraints of the reverse prosthesis, or, quite possibly reflect the typically older age and more sedentary lifestyle of patients who are indicated for reverse shoulder arthroplasty. In addition, if the patient had a preoperative expectation of return to recreational and sports activities as part of their normal way of life, their final results demonstrated better overall outcomes. Shoulder arthroplasty surgeons should be concerned about the outcomes desired by our patients, and the results that provide true value to their lives. We are now more aware of the activities that they are going to return to, whether we recommend restrictions or not

Introduction. Progressive resistance training (PRT) as a mean to reduce symptoms in patients with hip dysplasia (HD) has not yet been tried out. The aim of this study was to examine if PRT is feasible in patients with HD. A secondary purpose was to report data on changes of patient reported outcomes, muscle performance and hip muscle strength following PRT. Materials and methods. Patients diagnosed with HD on the waiting list for a periacetabular osteotomy (PAO) were offered to participate in a PRT feasibility study. The PRT intervention consisted of 8-weeks of supervised PRT consisting of 20 training sessions with exercises for the hips and knees. Feasibility was evaluated as adherence, the number of dropouts and adverse events. Furthermore, pain was reported after each exercise and one day after a training session using a 100mm visual analog scale (VAS). Pain was categorized as “safe” (VAS ≤20), “acceptable” (VAS >20–50) and “high risk” (VAS >50). Pre- and post the intervention patients completed the Copenhagen Hip and Groin Outcome Score (HAGOS), performed two hop-tests on each leg and had their peak torque of the hip extensors and flexors assessed by isokinetic dynamometry. Results. 16 patients, mean age 28 (range 22–40) years, completed the PRT intervention. Adherence was high (90.3% ±9.0%). Acceptable pain levels (VAS ≤50) were reported on average of 95% during the completed PRT sessions and after 92.3% of the sessions when assessed on the following day. Four out of six HAGOS subscales improved (P <0.05) after the intervention, as did standing distance jump and countermovement jump (8.3 cm 95% CI [1.2, 15.3], 1.8 cm [0.7, 2.9]) on the affected side. Dynamometry showed significant improved peak torque during isokinetic concentric hip flexion (15.8 Nm 95% CI [5.9, 25.8]) on the affected side. A similar improvement was seen during isometric hip flexion on the non-affected side. Conclusion. Supervised preoperative PRT is feasible in terms of drop outs, adherence, adverse events and pain levels in patients with HD scheduled for PAO. Furthermore, this feasibility study suggests that PRT may improve pain levels, patient reported outcomes, functional performance and hip flexion muscle strength

Purpose and Background. Strengthening the lumbar extensor musculature is a common recommendation for CLBP. Although reported as effective, variability in response in CLBP populations is not well investigated. This study investigated variability in responsiveness to isolated lumbar extension (ILEX) resistance training in CLBP participants by retrospective analysis of 3 RCTS. Methods and Results. Data from 77 intervention participants was available (males = 43, females = 34) 37 control participants (males = 20, females = 17). Intervention participants all underwent 12wks of ILEX resistance training and changes in ILEX strength, pain (VAS) and disability (ODI) measured. True inter-individual response variability was examined through calculation of difference in the standard deviation of change scores for both control and intervention. Intervention participants were classified into using k-means cluster analysis for strength changes and using MCIC cut-offs for VAS and ODI. Analysis suggested true inter-individual responses to the intervention existed. Participants were classified for strength changes as low (n = 31), medium (n = 36), and high responders (n = 10). Participants were classified for VAS changes as negative (n = 3), non-responders (n = 34), responders (n = 15), and high responders (n = 19). Participants were classified for ODI changes as negative (n = 2), non-responders (n = 21), responders (n = 29), and high responders (n = 25). Conclusion. Considerable variation exists in response to ILEX resistance training in CLBP. Future work should identify factors prognostic of successful outcomes. Conflicts of interest: None. Funding obtained: None

Objectives

The goals of this study were: 1) to determine if high-fat diet (HFD) feeding in female mice would negatively impact biomechanical and histologic consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate whether exercise and branched-chain amino acid (BCAA) supplementation would affect these parameters or attenuate any negative consequences resulting from HFD consumption.