This study investigated the effect of total joint arthroplasty (TJA) on arterial stiffness in patients with severe osteoarthritis (OA) compared to non-OA controls. A prospective cohort of 70 severe OA patients undergoing TJA (mean age 62 ± 7) and 82 age- and sex-matched controls without OA was followed over seven years. Aortic pulse wave velocity (aPWV), augmentation index (AIx), and central and peripheral haemodynamic parameters were measured using applanation tonometry (Sphygmocor) at baseline and follow-up. At baseline, the aPWV was significantly higher in the TJA group (p = 0.023). Over seven years, aPWV increased significantly in the control group, eliminating the between-group difference (9.3 ± 0.3 m/s in TJA vs. 9.3 ± 0.2 m/s in controls, p = 0.939). AIx was initially similar between groups, but was significantly lower in the TJA group at follow-up (p = 0.005). The increase in central diastolic blood pressure was also significantly smaller in the TJA group (p = 0.008). These results indicate that TJA may slow the progression of arterial stiffness and reduce central haemodynamic changes in severe OA patients compared to the general population.

BACKGROUND:We aimed to investigate metabolomic alterations in peripheral artery disease (PAD) by analyzing blood from the femoral artery and vein, assessing metabolite release/uptake in chronically ischemic lower limbs (PAD group) and nonischemic limbs (controls), and evaluating the representativeness of upper-limb venous samples. METHODS:In this exploratory case-control study, 24 patients with PAD (Fontaine IIb and III) and 18 control subjects with stable angina were enrolled. Blood was drawn from the femoral artery and vein, and the antecubital fossa. Metabolomic profiling of serum samples was performed using liquid chromatography and tandem mass spectrometry. We analyzed 560 metabolites, including amino acids and derivatives, acylcarnitines, ceramides, phosphatidylcholines, tri- and diglycerides, cholesteryl esters, sphingomyelins, and fatty acids, as well as 52 metabolic ratios/sums across various biochemical classes. RESULTS:Femoral arteriovenous (AV) concentration differences with in-group significance in at least one group and between-group significance was observed for 47 metabolites and five metabolic sums. Among these, eight metabolic variables in antecubital vein samples were significant. Correlation between AV differences and antecubital vein samples was weak. CONCLUSION:Using the femoral AV concentration differences of metabolites, we identified significant local metabolomic shifts in the PAD group. Most of these changes were not revealed using traditional upper-limb venous blood sampling. Further study of AV differences could improve the understanding of the pathophysiology of PAD.

OBJECTIVE:The clinical efficacy of remote ischaemic preconditioning (RIPC) remains unclear. This pilot study, a substudy of a randomised controlled trial, tested whether repeated RIPC reduces arterial stiffness, end organ damage, and oxidative stress in patients with intermittent claudication (IC). METHODS:In a single centre, randomised, sham controlled, double blind trial, 42 males with Fontaine stage IIa or IIb IC were allocated at a ratio of 1:1 to receive RIPC or sham using an automated device for 28 days in an outpatient setting (ClinicalTrials.gov ID NCT05084066). Secondary outcomes included changes in augmentation index (AIx), heart rate corrected AIx, carotid-femoral pulse wave velocity (cf-PWV), and biomarkers for cardiac (high sensitivity troponin T [hs-TnT], N-terminal pro B-type natriuretic peptide [NT-proBNP]), renal (creatinine, urea, cystatin C, β2 microglobulin, neutrophil gelatinase associated lipocalin, kidney injury molecule 1), and oxidative stress (high sensitivity C reactive protein, interleukin-6, interleukin-18, myeloperoxidase, adiponectin, oxidised low density lipoprotein). RESULTS:Data from 41 patients (RIPC n = 23, sham n = 18) aged 64.9 ± 7.4 years were analysed. The median change in cf-PWV was 0.2 m/s (interquartile range [IQR] -0.6, 0.6) in the RIPC group vs. 0.2 m/s (IQR -0.3, 0.8) in the sham group (p = .54). The median change in hs-TnT was 0 ng/L (IQR -1, 2) in the RIPC group vs. 1 ng/L (IQR -1, 2) in the sham group (p = .54). NT-proBNP showed a median change of -7 ng/L (IQR -32, 18) in the RIPC group vs. 6 ng/L (IQR -14, 35) in the sham group (p = .14). No statistically significant differences were observed between groups for arterial stiffness, oxidative stress, or renal biomarkers. CONCLUSION:Repeated RIPC did not significantly alter arterial stiffness, end organ damage, or oxidative stress biomarkers compared with sham treatment. It is possible that patients with IC already experience repeated RIPC from their ischaemic legs, thereby attenuating any additional effects from arm induced RIPC.

Total hip arthroplasty (THA) is an effective treatment for severe osteoarthritis. However, THA has a high surgical risk for patients with concomitant diseases and is associated with several serious complications, such as myocardial infarction, acute kidney injury and cognitive dysfunction. This study will explore the potential protective effects of remote ischaemic preconditioning (RIPC) in cemented THA patients. The PRINCIPAL study is designed as a randomised, controlled, parallel-group, blinded trial to assess the impact of RIPC in cemented THA patients. The study will compare two patient groups-one group will have the RIPC procedure, and the second will have the sham procedure. The primary outcome is the peak troponin T concentration during the three postoperative days. Secondary outcomes include markers of arterial stiffness (augmentation index (AIx), carotid-femoral pulse wave velocity, central blood pressures), neural (neuron-specific enolase, S100B) and renal injury biomarkers (estimated glomerular filtration rate, creatinine, cystatin C), markers of systemic inflammation (hypoxia-inducible factor 1-alpha, interleukin (IL)-6, IL-1β, tumour necrosis factor-alpha, IL-10) and oxidative stress (total peroxide concentration, total antioxidant capacity), as well as clinical outcome measures such as major adverse cardiovascular events and all-cause mortality. The ethical board of the University of Tartu has granted approval for the study (no. 384T-26). The results of this study will be disseminated in international peer-reviewed journals. NCT06323018.

OBJECTIVE:Remote ischaemic preconditioning (RIPC) is a promising non-invasive strategy in which brief episodes of ischaemia and reperfusion can increase skeletal muscle resistance to ischaemia and improve mobility. This study aimed to determine whether 28 consecutive days of RIPC improved intermittent claudication (IC) symptoms compared with sham intervention. METHODS:This single centre, parallel, randomised, sham controlled, double blind trial was conducted from January 2022 to April 2023 in outpatient settings. Forty two patients with stable IC Fontaine stage IIa or IIb were randomised to RIPC or sham for 28 days. The pre-specified primary outcome was a change in the maximum walking distance (MWD) after 28 days measured with a treadmill test. A > 10% change in MWD was considered clinically significant. Change in intermittent claudication distance (ICD), time to relief from claudication (TRC), and health related quality of life (HRQoL) measured with the VascuQoL-6 questionnaire were the secondary outcomes (ClinicalTrials.gov ID: NCT05084066). RESULTS:Forty one men (RIPC = 23, sham = 18) aged 64.9 ± 7.4 years were analysed. A change of > 10% in MWD occurred in 14 patients in the RIPC group vs. eight patients in the sham group (relative risk 1.37, 95% confidence interval 0.74 - 2.25; p = .35). Changes in ICD, TRC, and HRQoL between the groups were not statistically significant. CONCLUSION:In this trial, RIPC did not significantly improve MWD, ICD, or TRC compared with treatment with a sham device.

Resistance exercise has been shown to have a beneficial effect on muscular strength, bone mineral density, and body composition. Nevertheless, there is less evidence to demonstrate a protective effect of resistance exercise on cardiovascular health, particularly on blood pressure (BP) and cardiac function in competitive powerlifting athletes. PURPOSE: To evaluate the effect of 12-week strength training program (STP) on arterial stiffness, blood pressure and cardiac function in well-trained powerlifting athletes. METHODS: 19 well-trained male powerlifters (28.2 ± 6.1 yrs; 179.2 ± 5.9 cm¸ 99.9 ± 16.5 kg; BMI 31.2 ± 5.1) exercised for 12 weeks, 4 days per week with an intensity of 60-90% assessed from 1 RM and 90-120 min per session. Before the STP, there was an 8-week off-season period, where systematic strength training sessions and competitions were not allowed. Brachial BP was measured using standard protocol (OMRON M4-I, Omron Healthcare Europe BV, Netherlands); carotid-femoral pulse wave velocity (cfPWV) and central blood pressure were measured by applanation tonometry using the SphygmoCor device (AtCor Medical, Sydney, Australia), and an echocardiographic examination (Sonos7500, Philips Medical Systems, Inc., Highland Heights, OH, USA) was performed. All the measurements were performed at baseline and after 12-week STP. RESULTS: Subjects’ mean brachial and central systolic BP decreased significantly after the training period (132.3 ± 8.8 vs 124.3 ± 8.7 mmHg, p < 0.01 and 110.1 ± 7.7 vs 104.5 ± 8.7 mmHg, p < 0.01, respectively). There were no significant differences after the training period in cfPWV. Echocardiographic parameters showed that strength training significantly improved systolic tricuspid annular velocity (p < 0.01) and mitral E/e’ ratio (p < 0.05). CONCLUSION: 12-week strength training program had a beneficial effect on brachial and central systolic blood pressure and improved left and right ventricular cardiac function in male well-trained powerlifting athletes. There was no effect of strength training on arterial stiffness. Study was supported by Institutional Research Fundings No. IUT 02-7 and PRG435.

Introduction: Aortoenteric fistulas (AEF) are infrequent malignant complications of abdominal aortic aneurysms (AAA). We present a unique case of a patient with recurring AAA fistulisations. Presentation of case: During oncologic treatment, a 63-year-old male was incidentally diagnosed with infrarenal AAA and assigned follow-up but was hospitalised with anaemia and elevated inflammation markers 14 months later. A CT-angiography scan detected an AAA enlargement, but no extravasation (negative FOBT). Another CTAscan displayed a pseudoaneurysm and ruptured AAA 10 days later. During a total laparotomy, an enlarged pulsating inflammatory conglomerate without active leakage was detected, with a 2 cm duodenal defect (PAEF). The AAA was resected and replaced by a linear silver-coated Dacron graft. 3,5 years after PAEF, the patient was hospitalised with abdominal pain and haematemesis. He underwent gastroscopies, coloscopies, CT- and CTA-scans - all without significant findings. Only after the capsule-endoscopy detected a jejunal ulcer, the PET-scan visualized active regions in the jejunum and the aortic graft. A total laparotomy was performed; previous stapler-lined jejuno-jejunal anastomosis had adhered to the silver-coated Dacron graft (SAEF). The Dacron graft was removed and replaced with a linear xenograft from bovine pericardium. Discussion: No evidence-based recommendations prefer endovascular aneurysm repair (EVAR) over open repair, leaving the strategy dependent on local preferences. Whether EVAR or initial xenograft usage would have shown surpassing results, is speculative, as no graft material/type has proved long-term pre-eminence. Conclusions: This case displays AEF's complex treatment and challenging diagnosis. Multimodal diagnostic and strategic approaches should be considered for best patient outcome.

Remote ischemic preconditioning (RIPC) has demonstrated protective effects in patients with lower extremity arterial disease (LEAD) undergoing digital subtraction angiography (DSA) and/or percutaneous transluminal angioplasty (PTA). This study aimed to investigate the impact of RIPC on the metabolomical profile of LEAD patients undergoing these procedures and to elucidate its potential underlying mechanisms. A total of 100 LEAD patients were enrolled and randomly assigned to either the RIPC group (n = 46) or the sham group (n = 54). Blood samples were drawn before and 24 h after intervention. Targeted metabolomics analysis was performed using the AbsoluteIDQ p180 Kit, and changes in metabolite concentrations were compared between the groups. The RIPC group demonstrated significantly different dynamics in nine metabolites compared to the sham group, which generally showed a decrease in metabolite concentrations. The impacted metabolites included glutamate, taurine, the arginine-dimethyl-amide-to-arginine ratio, lysoPC a C24:0, lysoPC a C28:0, lysoPC a C26:1, PC aa C38:1, PC ae C30:2, and PC ae C44:3. RIPC exhibited a 'stabilization' effect, maintaining metabolite levels amidst ischemia-reperfusion injuries, suggesting its role in enhancing metabolic control. This may improve outcomes for LEAD patients. However, additional studies are needed to definitively establish causal relationships among these metabolic changes.

Background and Aims: Remote ischemic preconditioning (RIPC) is a procedure that aims to reduce ischemia-reperfusion injury to ischemia-sensitive organs. Metabolomics is a novel method to explain the effects of RIPC and draw conclusions about its usefulness in clinical practice. This study assesses whether preoperative RIPC affects metabolome after vascular surgery and if these metabolomic changes correlate with heart and kidney injury markers. Methods: A randomized-controlled, double-blinded trial was carried out in the Tartu University Hospital. Patients undergoing elective vascular surgery were recruited. RIPC consisting of four cycles of 5 minutes of ischemia followed by 5 minutes of reperfusion, was applied before the surgery. Blood samples were collected preoperatively and approximately 24 hours postoperatively. The metabolome was analyzed with the AbsoluteIDQ p180 Kit. Results: Final analysis included 45 patients from the RIPC and 47 from the sham group. Mean age was 67 (± 9) and 66 (± 10) years in the RIPC and sham groups, respectively (p=0.577). RIPC did not cause significant changes in metabolites 24 hours after surgery. Positive linear correlation of change in the kynurenine/tryptophan ratio with change in hs-troponin T (r = 0.570, p ˂0.001), NT-proBNP (r = 0.552, p ˂0.001), cystatin C (r = 0.534, p <0.001) and beta-2-microglobulin (r = 0.504, p ˂0.001) were detected only in the RIPC group. Conclusions: RIPC did not provoke significant changes in metabolome 24 hours after vascular surgery. The positive linear correlation between the kynurenine/tryptophan ratio and heart and kidney injury markers suggests that the Kynurenine-Tryptophan pathway can play a role in RIPC-associated cardio- and renoprotective effects.

Background and objective: Current evidence suggests short-term survival benefit from endovascular aneurysm repair (EVAR) versus open surgical repair (OSR) in elective abdominal aortic aneurysm (AAA) procedures, but this benefit is lost during long-term follow-up. The aim of this study was to compare short- and mid-term all-cause mortality in patients with non-ruptured aneurysm treated by OSR and EVAR; and to assess the rate of complications and reinterventions, as well as to evaluate their impact on survival. Methods: The medical records of the non-ruptured AAA patients undergoing OSR or EVAR between 1 January 2011 and 31 December 2019 at Tartu University Hospital, Estonia, were retrospectively reviewed. We gathered survival data from the national registry (mean follow-up period was 3.7 ± 2.3 years). Results: A total of 225 non-ruptured AAA patients were treated operatively out of whom 95 (42.2%) were EVAR and 130 (57.8%) were OSR procedures. The difference in estimated all-cause mortality between the OSR and EVAR groups at day 30 was statistically irrelevant (2.3% vs 0%; p = 0.140), but OSR patients showed statistically significantly higher 5 year survival compared with EVAR patients (75.3% vs 50.0%, p = 0.002). Complication and reintervention rates for the EVAR and OSR groups did not differ statistically (26.3% vs 16.9%, p = 0.122; 10.5% vs 11.5%, p = 0.981, respectively). Multivariate analysis revealed that greater aneurysm diameter (p = 0.012), EVAR procedure (p = 0.016), male gender (p = 0.023), and cerebrovascular diseases (p = 0.028) were independently positively associated with 5-year mortality. Conclusions: Thirty-day mortality, and complication and reintervention rates for EVAR and OSR after elective AAA repair were similar. Although the EVAR procedure is an independent risk factor for 5-year mortality, higher age and greater proportion of comorbidities among EVAR patients may influence not only the choice of treatment modality, but also prognosis.

Background: remote ischemic preconditioning (RIPC) is a phenomenon in which short episodes of ischemia are applied to distant organs to prepare target organs for more prolonged ischemia and to induce protection against ischemia-reperfusion injury. This study aims to evaluate whether preoperatively performed RIPC affects the metabolome and to assess whether metabolomic changes correlate with heart and kidney injury markers after vascular surgery. Methods: a randomized sham-controlled, double-blinded trial was conducted at Tartu University Hospital. Patients undergoing elective open vascular surgery were recruited and RIPC was applied before operation. Blood was collected preoperatively and 24 h postoperatively. The metabolome was analyzed using the AbsoluteIDQ p180 Kit. Results: final analysis included 45 patients from the RIPC group and 47 from the sham group. RIPC did not significantly alter metabolites 24 h postoperatively. There was positive correlation of change in the kynurenine/tryptophan ratio with change in hs-troponin T (r = 0.570, p < 0.001), NT-proBNP (r = 0.552, p < 0.001), cystatin C (r = 0.534, p < 0.001) and beta-2-microglobulin (r = 0.504, p < 0.001) only in the RIPC group. Conclusions: preoperative RIPC did not significantly affect the metabolome 24 h after vascular surgery. The positive linear correlation of kynurenine/tryptophan ratio with heart and kidney injury markers suggests that the kynurenine–tryptophan pathway can play a role in RIPC-associated cardio- and nephroprotective effects.

Arterial stiffness (AS) is one of the earliest detectable signs of structural and functional alterations of the vessel wall and an independent predictor of cardiovascular events and death. The emerging field of metabolomics can be utilized to detect a wide spectrum of intermediates and products of metabolism in body fluids that can be involved in the pathogenesis of AS. Research over the past decade has reinforced this idea by linking AS to circulating acylcarnitines, glycerophospholipids, sphingolipids, and amino acids, among other metabolite species. Some of these metabolites influence AS through traditional cardiovascular risk factors (e.g., high blood pressure, high blood cholesterol, diabetes, smoking), while others seem to act independently through both known and unknown pathophysiological mechanisms. We propose the term ‘arteriometabolomics’ to indicate the research that applies metabolomics methods to study AS. The ‘arteriometabolomics’ approach has the potential to allow more personalized cardiovascular risk stratification, disease monitoring, and treatment selection. One of its major goals is to uncover the causal metabolic pathways of AS. Such pathways could represent valuable treatment targets in vascular ageing.

OBJECTIVE:To estimate the incidence of acute mesenteric ischaemia (AMI), proportions of its different forms and short-term and long-term mortality.DESIGN:Systematic review and meta-analysis.DATA SOURCES:MEDLINE (Ovid), Web of Science, Scopus and Cochrane Library were searched until 26 July 2022.ELIGIBILITY CRITERIA:Studies reporting data on the incidence and outcomes of AMI in adult populations.DATA EXTRACTION AND SYNTHESIS:Data extraction and quality assessment with modified Newcastle-Ottawa scale were performed using predeveloped standard forms. The outcomes were the incidence of AMI and its different forms in the general population and in patients admitted to hospital, and the mortality of AMI in its different forms.RESULTS:From 3064 records, 335 full texts were reviewed and 163 included in the quantitative analysis. The mean incidence of AMI was 6.2 (95% CI 1.9 to 12.9) per 100 000 person years. On average 5.0 (95% CI 3.3 to 7.1) of 10 000 hospital admissions were due to AMI. Occlusive arterial AMI was the most common form constituting 68.6% (95% CI 63.7 to 73.2) of all AMI cases, with similar proportions of embolism and thrombosis.Overall short-term mortality (in-hospital or within 30 days) of AMI was 59.6% (95% CI 55.5 to 63.6), being 68.7% (95% CI 60.8 to 74.9) in patients treated before the year 2000 and 55.0% (95% CI 45.5 to 64.1) in patients treated from 2000 onwards (p<0.05). The mid/long-term mortality of AMI was 68.2% (95% CI 60.7 to 74.9). Mortality due to mesenteric venous thrombosis was 24.6% (95% CI 17.0 to 32.9) and of non-occlusive mesenteric ischaemia 58.4% (95% CI 48.6 to 67.7). The short-term mortality of revascularised occlusive arterial AMI was 33.9% (95% CI 30.7 to 37.4).CONCLUSIONS:In adult patients, AMI is a rarely diagnosed condition with high mortality, although with improvement of treatment results over the last decades. Two thirds of AMI cases are of occlusive arterial origin with potential for better survival if revascularised.PROSPERO REGISTRATION NUMBER:CRD42021247148.

Purpose: Metabolomic analysis holds great potential for improving the understanding about osteoarthritis (OA) caused metabolomic shifts associated with systemic inflammation and oxidative stress (OxS). Amino acids and polyamines are closely involved in maintaining the balance between reactive oxygen species (ROS) and antioxidant system. The main aim of the study was to map the systemic changes of amino acids and polyamines in the severe OA compared with asymptomatic matched controls and identify systemic serum biomarkers that have the potential to be used in clinical practise. Methods: Knee and hip OA patients who met the American College of Rheumatology criteria for knee and hip OA were included in the study. The study participants were recruited prospectively. The control group was matched to age and gender and recreuited from the family medicine practices. The exclusion criteria were posttraumatic OA, infectious arthropathy, endocrine arthropathy, malignancy, acute inflammatory disease, insufficiency of kidneys (eGFR < 60ml/min/1.73m2), clinically significant heart failure, diabetes. The fasting serum of 70 knee and hip OA patients and 82 controls were assessed via targeted approach using the AbsoluteIDQ™ p180 kit. The blood samples were collected in the morning after an overnight fast and abstinence from tobacco and alcohol. The samples were held in at -70 °C until assessment. Standard preoperative radiographs were used for the grading of OA severity according to Kellgren and Lawrence by two independent raters. A consensus score was used for the analysis.The level of metabolites (amino acids and polyamines) has been expressed as μM ± standard deviation. Results: The two study groups had similar age and gender proportions, but OA group had significantly higher BMI. Inflammatory markers (white blood cell count and high sensitivity C-reactive protein) were higher in the OA group.Tabled 1General description of study groupsOsteoarthritis (n=70)Controls (n=82)p-valueAge (years)62 ± 761 ± 80.173Male/Female (n)36 / 3438 / 440.871BMI (kg/m2)27.8 ± 3.226.0 ± 3.50.001hs-CRP (mg/l)1.9 ± 1.11.5 ± 1.20.014WBC (109/l)6.5 ± 1.45.7 ± 1.90.001 Open table in a new tab There were several significant differences in the amino acid and polyamine levels across the study groups. The present study demonstrates significantly higher levels of arginine (Arg), asparagine (Asn), leucine (Leu), serine (Ser), asymmetric dimethylarginine (ADMA), phenylalanine (Phe), spermidine and lower levels of serotonin and spermine/spermidin ratio in the OA group after adjusting for BMI.Tabled 1Amino acid and polyamine levels of the study groupsOsteoarthritis (n=70)Controls (n=82)p-valueArginine105.2 ± 22.496.3 ± 23.50.020Glycine280.8 ± 116.2289.8 ± 114.60.794Leucine180.9 ± 50.0156.7 ± 39.50.008ADMA0.618 ± 0.1560.559 ± 0.1330.037Spermidine0.188 ± 0.0510.161 ± 0.0460.001Spermine0.158 ± 0.0140.159 ± 0.0160.677Spermine-spermidine ratio0.898 ± 0.2271.060 ± 0.279<0.001Serine137.4 ± 29.1121.8 ± 27.60.001 Open table in a new tab Several changes in the serum levels of amino acids of the OA patients compared with controls suggest systemic inflammation in severe OA patients. We found increased levels of Arg and ADMA in OA group and the severity of OA was correlated to Arg levels. Arg remained an independent determinant of OA severity in the multiple regression model after including potential covariates. The increase of 1 grade in the radiographic OA severity was equal to an average of 10.0 μM higher level of serum Arg. ADMA and Arg play important role in nitric oxide (NO) production. Arg is the precursor for NO and ADMA is the major endogenous inhibitor of NO synthase (NOS). The combination of increased Arg and ADMA levels in OA group suggest inhibited NOS activity that leads to Arg accumulation. NO has been linked to inflammation in OA pathogenesis and also anabolic mechanisms so the specific details remain to be elucidated in further research.Tabled 1Regression model with arginine as the dependent variable in the osteoarthritis patients groupBStd ErrorBetap- valueOA severity9.124.10.280.031Gender5.775.60.130.310Age-0.310.37-0.100.392BMI-0.240.86-0.0330.782Glucose-7.114.15-0.210.092 Open table in a new tab We found that OA patients had higher levels of Ser and severe OA was associated with lower levels of serum Gly. The correlation was further analyzed in a multiple regression model and remained independent after including potential covariates. An increase of 1 grade in the radiographic OA severity was equal to an average of 46.4 μM of lower level of Gly in the OA group. The changes indicate Gly deficiency and Ser accumulation in the severe OA that might be related to enzyme Ser hydroxymethyltranferase impairment and lead to decreased collagen synthesis in the affected joint. Ser hydroxymethyltranferase activity has been also found to be altered in metabolic syndrome and obesity, conditions that are closely related to OA.Tabled 1Regression model with glycine as the dependent variable in the osteoarthritis patients groupBStd ErrorBetap- valueOA severity-43.220.6-0.250.040Gender-64.728.1-0.280.025Age0.51.80.030.777BMI3.04.30.080.483Glucose-25.320.7-0.150.227 Open table in a new tab The significantly higher Leu levels in OA might reflect the increased collagen breakdown due to cartilage degeneration and muscle atrophy. Furthermore, lower spermin to spermidine ratio and increased spermidine in the OA group might indicate excessive OxS in OA. The spermine-spermidine system protects against OxS by scavenging free radicals. The increased level of spermidine in OA patients might be caused by lower activity of spermine synthase, an enzyme that converts spermidine to spermine. The accumulation of spermidine might impair the lysosome function, thus leading to increased OxS. Conclusions: The present study demostrates significant changes in the amino acid and polyamine profiles of OA patients that highlight the role of inflammation and excessive OxS in the pathogenesis of OA.