Selenoprotein P increases upon selenium and coenzyme Q10 supplementation and is associated with telomere length, quality of life and reduced inflammation and mortality.

BACKGROUND: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease. OBJECTIVE: To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q10 supplementation on SELENOP. METHODS: SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day), or placebo. Pre-intervention, the average serum selenium level was 67 µg/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated. RESULTS: Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 µg/L, and for GPx3 at 99 µg/L. Supplementation induced higher levels of SELENOP. CONCLUSION: Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects.

Intravenous anti-P. aeruginosa IgY-antibodies do not decrease pulmonary bacterial concentrations in a porcine model of ventilator-associated pneumonia.

Ventilator associated pneumonia (VAP) caused by P. aeruginosa is a cause of morbidity and mortality in critically ill patients. The spread of pathogens with anti-microbial resistance mandates the investigation of novel therapies. Specific polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) might be effective for VAP caused by P. aeruginosa. The objective of this study was to investigate if intravenous Pa-IgY decreases the lower airway concentration of P. aeruginosa in VAP. We used a double blind randomized placebo controlled porcine model of VAP caused by P. aeruginosa. Eighteen pigs were randomized to either receive intravenous Pa-IgY or placebo. Repeated registration of physiological parameters and sampling was performed for 27 h. Concentration of P. aeruginosa in BAL-cultures was similar in both groups with 104.97 ± 102.09 CFU/mL in the intervention group vs 104.37 ± 102.62 CFU/mL in the control group at the end of the experiment. The intervention group had higher heart rate, cardiac index, oxygen delivery and arterial oxygen tension/fraction of inspired oxygen-ratio, but lower plasma lactate and blood hemoglobin levels than the control group. In summary, in an anesthetized and mechanically ventilated porcine model of VAP, Pa-IgY at the dose used did not decrease concentrations of P. aeruginosa in the lower airways.

Effects of denosumab treatment on the expression of receptor activator of nuclear kappa-B ligand (RANKL) and TNF-receptor TNFRSF9 after total hip arthroplasty-results from a randomized placebo-controlled clinical trial.

We investigated whether the drug denosumab modulates the inflammatory response after total hip arthroplasty in a randomized controlled trial. Significantly increased expression of RANKL was found in patients treated with denosumab. This could provide an explanation for the rebound effect with rapid loss of BMD seen after discontinuation of denosumab treatment. PURPOSE: To evaluate whether denosumab, a human monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand (RANKL), modulates the inflammatory response after cementless total hip arthroplasty (THA) in patients with osteoarthritis of the hip. METHODS: Sixty-four patients operated with cementless THA were randomized to two doses of 60-mg denosumab or placebo 1-3 days and 6 months postoperatively. Serum samples were analyzed by a multiplex extension assay detecting 92 inflammation-related proteins. Bone turnover markers were assessed. Proteins were analyzed using linear mixed effect models. Validation of conspicuous findings was performed with ELISA. RESULTS: Two proteins were significantly affected by denosumab treatment: RANKL and tumor necrosis factor receptor super family member 9 (TNFRSF9). Serum levels of RANKL were more than twice as high in the denosumab than in the placebo group 3 months after surgery (ratio 2.10, p<0.001). Six and 12 months after surgery, the expression of RANKL was still elevated in the denosumab-treated group (ratios 1.50, p < 0.001; 1.47, p =0.002). The expression of TNFRSF9 was lower in the denosumab group at 3 months (ratio 0.68, p<0.001). In the denosumab group, concentrations of bone turnover markers were substantially reduced after 3 months, remained suppressed after 6 and 12 months, but increased above baseline at 24 months after surgery. CONCLUSION: Two subcutaneous denosumab injections 6 months apart increase RANKL and depress TNFRSF9 after THA. This provides a possible explanation for the rebound effect on bone turnover markers as well as bone mineral density (BMD) upon withdrawal of denosumab. None of the other measured markers of inflammation was influenced by denosumab treatment.

Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress.

Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.

Using the Goldilocks Principle to model coral ecosystem engineering.

The occurrence and proliferation of reef-forming corals is of vast importance in terms of the biodiversity they support and the ecosystem services they provide. The complex three-dimensional structures engineered by corals are comprised of both live and dead coral, and the function, growth and stability of these systems will depend on the ratio of both. To model how the ratio of live : dead coral may change, the 'Goldilocks Principle' can be used, where organisms will only flourish if conditions are 'just right'. With data from particle imaging velocimetry and numerical smooth particle hydrodynamic modelling with two simple rules, we demonstrate how this principle can be applied to a model reef system, and how corals are effectively optimizing their own local flow requirements through habitat engineering. Building on advances here, these approaches can be used in conjunction with numerical modelling to investigate the growth and mortality of biodiversity supporting framework in present-day and future coral reef structures.

Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients.

BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.

Plasma perfluoroalkyls are associated with decreased levels of proteomic inflammatory markers in a cross-sectional study of an elderly population.

Perfluoroalkyl substances (PFAS) have been linked to immunotoxicity in experimental studies. Although PFAS exposure is associated with altered immune response in epidemiological studies of children, it is less known whether this is observed also in elderly adults. Eight PFAS and 86 proteins were measured in plasma from 965 elderly individuals from Sweden (all aged 70, 50% women). PFAS were measured using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry. Proteins were measured using a multiplex proximity extension assay (PEA) and covered among others inflammatory marker proteins such as monocyte chemoattractant proteins, tumor necrosis factors, and interleukins. We examined cross-sectional associations using multivariable linear regression at two levels of adjustment. We observed significant decreases in levels of 24 proteins in relation to a ln-unit increase in PFAS concentrations following adjustment for sex, sample storage time in freezer, and correction for multiple testing. Associations of PFAS and hepatocyte growth factor (HGF) and macrophage colony-stimulating factor 1 (CSF-1) remained significant (p-value <0.05) following full covariate adjustment for smoking, exercise habits, education, energy, and alcohol intake, body mass index (BMI), glomular filtration rate (GFR) as well as corticoid- and COX-inhibitor treatment. CSF-1 was inversely associated with perfluorohexane sulfonic acid (PFHxS) ß: -0.08: 95% confidence interval (CI); -0.13, -0.02), perfluorooctanoic acid (PFOA) ß: -0.04: 95% CI; -0.07, -0.006, perfluorononanoic acid (PFNA) ß: -0.04: 95% CI; -0.08, -0.003, perfluorodecanoic acid (PFDA) ß: -0.03: 95% CI; -0.06, -0.003, and perfluoroundecanoic acid (PFUnDA) ß: -0.05: 95% CI; -0.08, -0.02. The magnitude and direction of PFAS vs protein relationships were similar also for HGF. Our findings implicate PFAS exposure with decreased levels of proteomic markers of inflammation in elderly humans.

Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients.

PURPOSE: The aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients. MATERIAL AND METHODS: We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75-100 IU/kg subcutaneously). RESULTS: Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity. CONCLUSIONS: Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties.

Identification and toxicological evaluation of cyclic sulfonium ion degradation products of sulphur mustard.

In the aftermath of WWII large amount seized German chemical munitions were dumped in the Baltic Sea by Allied forces. In this work, we have compared the chemical content of the solidified blocks of dumped WWII mustard gas collected from the Baltic Sea with solid precipitate from stored mustard gas, known as heel. We have identified the same cyclic sulfonium ions in both samples. In assessing the environmental and toxicological impact of dumped sulphur mustard munitions on the world's oceans the potential risk posed by cyclic sulphur mustard salts have so far not been incorporated. The toxicity of 1-(2-chloroethyl)-1,4-dithiane and its hydrolysis product 1-(2-hydroxyethyl)- 1,4-dithiane was evaluated using three different cell lines. Their effect on released pro-inflammatory cytokines was also measured. The toxicity tests showed low toxicity and low pro-inflammatory response and we therefore conclude that the environmental threat posed by these compounds is low.

An electrochemical cell for 2-dimensional surface optical reflectance during anodization and cyclic voltammetry.

We have developed an electrochemical cell for in situ 2-Dimensional Surface Optical Reflectance (2D-SOR) studies during anodization and cyclic voltammetry. The 2D-SOR signal was recorded from electrodes made of polycrystalline Al, Au(111), and Pt(100) single crystals. The changes can be followed at a video rate acquisition frequency of 200 Hz and demonstrate a strong contrast between oxidizing and reducing conditions. Good correlation between the 2D-SOR signal and the anodization conditions or the cyclic voltammetry current is also observed. The power of this approach is discussed, with a focus on applications in various fields of electrochemistry. The combination of 2D-SOR with other techniques, as well as its spatial resolution and sensitivity, has also been discussed.

TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department.

BACKGROUND: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. AIM: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea. POPULATION AND METHODS: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP. RESULTS: Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56). CONCLUSIONS: We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.

Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial.

BACKGROUND: Studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss and recovery. Only one randomized study is available, which showed enhanced functional recovery after LDP compared with ODP. METHODS: Consecutive patients evaluated at a multidisciplinary tumour board and planned for standard distal pancreatectomy were randomized prospectively to LDP or ODP in an unblinded, parallel-group, single-centre superiority trial. The primary outcome was postoperative hospital stay. RESULTS: Of 105 screened patients, 60 were randomized and 58 (24 women, 41 per cent) were included in the intention-to-treat analysis; there were 29 patients of mean age 68 years in the LDP group and 29 of mean age 63 years in the ODP group. The main indication was cystic pancreatic lesions, followed by neuroendocrine tumours. The median postoperative hospital stay was 5 (i.q.r. 4-5) days in the laparoscopic group versus 6 (5-7) days in the open group (P = 0·002). Functional recovery was attained after a median of 4 (i.q.r. 2-6) versus 6 (4-7) days respectively (P = 0·007), and duration of surgery was 120 min in both groups (P = 0·482). Blood loss was less with laparoscopic surgery: median 50 (i.q.r. 25-150) ml versus 100 (100-300) ml in the open group (P = 0·018). No difference was found in the complication rates (Clavien-Dindo grade III or above: 4 versus 8 patients respectively). The rate of delayed gastric emptying and clinically relevant postoperative pancreatic fistula did not differ between the groups. CONCLUSION: LDP is associated with shorter hospital stay than ODP, with shorter time to functional recovery and less bleeding. Registration number: ISRCTN26912858 ( www.isrctn.com).

ANTECEDENTES: Los estudios han sugerido que la pancreatectomía distal laparoscópica (laparoscopic dital pancreatectomy, LDP) resulta ventajosa en comparación con la pancreatectomía distal por vía abierta (open distal pancreatectomy, ODP) respecto a la estancia hospitalaria, pérdida sanguínea y recuperación. Solamente existe un estudio aleatorizado que muestra una mejor recuperación funcional después de la LDP en comparación con la ODP. MÉTODOS: En un ensayo de superioridad unicéntrico, abierto y de grupos paralelos, los pacientes consecutivos evaluados por el comité multidisciplinario de tumores y a los que se indicó una pancreatectomía distal estándar fueron asignados al azar de forma prospectiva a LDP o ODP. El resultado primario fue la estancia hospitalaria postoperatoria. RESULTADOS: De 105 pacientes evaluados, 60 fueron aleatorizados, de los cuales 58 pacientes (24 mujeres; 41%) fueron incluidos y asignados a LDP (n = 29; edad media 68 años) o ODP (n = 29; edad media 63 años) e incluidos en un análisis por intención de tratamiento. La principal indicación fueron las lesiones quísticas del páncreas seguida de los tumores neuroendocrinos. La estancia hospitalaria postoperatoria fue de 5 días (rango intercuartílico, interquartile range, IQR 4-5) en el grupo laparoscópico versus 6 (5-7) días en el grupo de cirugía abierta (P = 0,002). La recuperación funcional se alcanzó después de 4 (2-6) versus 6 (4-7) días (P = 0,007), y el tiempo operatorio fue de 120 minutos en ambos grupos (P = 0.48). Las pérdidas hemáticas fueron menores en la cirugía laparoscópica, 50 (25-150) versus 100 mL (100-300) (P = 0,018). No se hallaron diferencias en las tasas de complicaciones (grado Clavien-Dindo ≥ 3) con 4 versus 8 pacientes en el grupo laparoscópico y en el grupo abierto, respectivamente. La tasa de retraso en el vaciamiento gástrico y de fístula postoperatoria clínicamente relevante no difirió entre los grupos. CONCLUSIÓN: La pancreatectomía distal laparoscópica se asocia con una estancia hospitalaria más corta en comparación con la cirugía abierta, con un menor tiempo para la recuperación funcional y menos hemorragia.

Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status.

PURPOSE: Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 µg/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. METHODS: In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. RESULTS: The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. CONCLUSION: In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

Endostatin predicts mortality in patients with acute dyspnea - A cohort study of patients seeking care in emergency departments.

BACKGROUND: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported. AIM: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age. RESULTS: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95% CI 1.31-3.44 p < 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p < 0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin. CONCLUSIONS: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3%.

Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits.

AIM: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. METHODS: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8-9 m/kg body weight) for an additional 3 h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNFα IL-6 and IL-8 in lung homogenates were evaluated. RESULTS: Both surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1 h, P/F ratio and PaO2 at 1.5 h compared to rSP-C33Leu surfactant. CONCLUSION: This study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

Correction to: Inhalation of specific anti-Pseudomonas aeruginosa IgY antibodies transiently decreases P. aeruginosa colonization of the airway in mechanically ventilated piglets.

Following publication of the original article [1], the authors flagged that an incorrect piece of data is given in the Materials and Methods section of the article.

Hyaluronan concentration and molecular mass in psoriatic arthritis: biomarkers of disease severity, resistance to treatment, and outcome.

Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab. Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients' assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined. Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution. Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.