Amiloride lowers plasma TNF and interleukin-6 but not interleukin-17A in patients with hypertension and type 2 diabetes.

Interleukin (IL)-17A contributes to hypertension in preclinical models. T helper 17 and dendritic cells are activated by NaCl, which could involve the epithelial Na+ channel (ENaC). We hypothesized that the ENaC blocker amiloride reduces plasma IL-17A and related cytokines in patients with hypertension. Concentrations of IL-17A, IFN-γ, TNF, IL-6, IL-1ß, and IL-10 were determined by immunoassays in plasma from two patient cohorts before and after amiloride treatment: 1) patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension (n = 69, amiloride 5-10 mg/day for 8 wk) and 2) patients with hypertension and type 1 diabetes mellitus (T1DM) (n = 29) on standardized salt intake (amiloride 20-40 mg/day, 2 days). Plasma and tissue from ANG II-hypertensive mice with T1DM treated with amiloride (2 mg/kg/day, 4 days) were analyzed. The effect of amiloride and benzamil on macrophage cytokines was determined in vitro. Plasma cytokines showed higher concentrations (IL-17A ∼40-fold) in patients with T2DM compared with T1DM. In patients with T2DM, amiloride had no effect on IL-17A but lowered TNF and IL-6. In patients with T1DM, amiloride had no effect on IL-17A but increased TNF. In both cohorts, blood pressure decline and plasma K+ increase did not relate to plasma cytokine changes. In mice, amiloride exerted no effect on IL-17A in the plasma, kidney, aorta, or left cardiac ventricle but increased TNF in cardiac and kidney tissues. In lipopolysaccharide-stimulated human THP-1 macrophages, amiloride and benzamil (from 1 nmol/L) decreased TNF, IL-6, IL-10, and IL-1ß. In conclusion, inhibition of ENaC by amiloride reduces proinflammatory cytokines TNF and IL-6 but not IL-17A in patients with T2DM, potentially by a direct action on macrophages.NEW & NOTEWORTHY ENaC activity may contribute to macrophage-derived cytokine release, since amiloride exerts anti-inflammatory effects by suppression of TNF and IL-6 cytokines in patients with resistant hypertension and type 2 diabetes and in THP-1-derived macrophages in vitro.

Late-onset delirious mania: Does it ring a bell?

BACKGROUND: Bell's mania was first described in 1849, and other terms have been used to describe this condition, including delirious mania, mania with delirium, and excited delirium. However, no international diagnostic manual has included mania as an independent diagnostic tool. The criteria for delirious mania were proposed by Bond et al. METHODS: We present a case of a man without a personal or family psychiatric history who experienced his first manic episode of delirium and psychosis at 76 years old. CONCLUSIONS: The case described in this study is compatible with mood disorders, the original description of Bell's mania, and Bond's definition of delirious mania. Although rare, extremely late-onset primary mania can occur without personal or family psychiatric history. The initial clinical presentation of delirium requires a thorough medical investigation, including magnetic resonance imaging (MRI) and lumbar puncture with neuronal antibodies. The addition of delirious mania to the group of bipolar disorders in future editions of The International Classification of Diseases (ICD) and Diagnostic and Statistical Manual of Mental Disorders (DSM) has therapeutic and prognostic implications. The Bond criteria can provide valuable information in this respect. Further investigations are necessary to clarify the pathophysiology and epidemiology of delirious mania.

Development of solid-state fermentation process of spent coffee grounds for the differentiated obtaining of chlorogenic, quinic, and caffeic acids.

BACKGROUND: Spent coffee grounds (SCGs) are a good source of chlorogenic acid (CGA), which can be hydrolyzed to quinic acid (QA) and caffeic acid (CA). These molecules have antioxidant and neuroprotective capacities, benefiting human health. The hydrolysis of CGA can be done by biotechnological processes, such as solid-state fermentation (SSF). This work evaluated the use of SSF with Aspergillus sp. for the joint release of the three molecules from SCGs. RESULTS: Hydroalcoholic extraction of the total phenolic compounds (TPCs) from SCGs was optimized, obtaining 28.9 ± 1.97 g gallic acid equivalent (GAE) kg-1 SCGs using 0.67 L ethanol per 1 L, a 1:9 solid/liquid ratio, and a 63 min extraction time. Subsequently, SSF was performed for 30 days, achieving the maximum yields for CGA, QA, and TPCs on the 16th day: 7.12 ± 0.01 g kg-1 , 4.68 ± 0.11 g kg-1 , and 54.96 ± 0.49 g GAE kg-1 respectively. CA reached its maximum value on the 23rd day, at 4.94 ± 0.04 g kg-1 . The maximum antioxidant capacity was 635.7 mmol Trolox equivalents kg-1 on the 14th day. Compared with unfermented SCGs extracts, TPCs and CGA increase their maximum values 2.3-fold, 18.6-fold for CA, 14.2 for QA, and 6.4-fold for antioxidant capacity. Additionally, different extracts' profiles were obtained throughout the SSF process, allowing us to adjust the type of enriched extract to be produced based on the SSF time. CONCLUSION: SSF represents an alternative to produce extracts with different compositions and, consequently, different antioxidant capacities, which is a potentially attractive fermentation process for different applications. © 2022 Society of Chemical Industry.

Achilles tendon gait dynamics after rupture: A three-armed randomized controlled trial comparing an individualized treatment algorithm vs. operative or non-operative treatment.

BACKGROUND: Individual treatment selection has been proposed as the key to optimized treatment. The purpose was to investigate if treatment selection using the individualized treatment algorithm Copenhagen Achilles Rupture Treatment Algorithm (CARTA) differs between patients treated as usual regarding gait dynamics and tendon elongation. METHODS: The patients were randomized to one of three parallel groups: 1) intervention group: participants treated according to CARTA, 2) control group: participants treated non-operatively, 3) control group: participants treated operatively. The primary outcome was ankle peak power during push off during walking at 12 months. RESULTS: 156 patients were assessed for eligibility. 21 were allocated to the intervention group, and 20 and 19 to the control groups. The results indicated no statistically significant differences between the intervention group and the control groups. CONCLUSIONS: Individualized treatment selection based on CARTA did not demonstrate less affected gait dynamics or less tendon elongation than patients treated as usual.

Treatment outcome at 1 year did not differ between use of cast or walker in the first 3 weeks after an acute Achilles tendon rupture. A registry study of 1304 patients from the Danish Achilles tendon database.

BACKGROUND: The best choice of orthosis in the treatment of acute Achilles tendon rupture is still under debate. OBJECTIVE: To investigate if choice of orthosis in the first 3 weeks of treatment affected patient reported outcome (Achilles tendon Total Rupture Score (ATRS)), tendon elongation (Achilles Tendon Resting Angle (ATRA) and Heel Rise Height (HRH)) and re-rupture. METHODS: Registry study in the Danish Achilles tendon Database. Patients treated with cast and patients treated with walker in the first 3 weeks of treatment were compared using a linear mixed-effects model adjusted for potential confounders. RESULTS: 1304 patients were included in the study. No clinically relevant difference was found: Adjusted mean difference (using walker the whole period as reference)(95% CI) ATRS after 1 year = 0.1(-3.0; 4.1), ATRS after 6 months = 2.0(-4.5; 5.8), ATRS after 2 years = 3.0(-0.7; 7.0), HRH difference = 0.6(-6.6; 8.2), ATRA difference = 0.03°(-1.5; 1.6), re-rupture(odds ratio) = 0.812(0.4; 1.61). CONCLUSION: Patients treated with cast the first 3 weeks after acute Achilles tendon rupture did not have better treatment outcome than patients treated with walker.

Dietary bovine milk miRNAs transported in extracellular vesicles are partially stable during GI digestion, are bioavailable and reach target tissues but need a minimum dose to impact on gene expression.

PURPOSE: Extracellular RNAs are unstable and rapidly degraded unless protected. Bovine-milk extracellular vesicles (EVs) confer protection to dietary miRNAs, although it remains unclear whether this importantly improves their chances of reaching host target cells to exert biological effects. METHODS: Caco-2, HT-29, Hep-G2 and FHs-74 cell lines were exposed to natural/labelled milk EVs to evaluate cellular uptake. Five frequently reported human milk miRNAs (miR-146b-5p, miR-148a-3p, miR-30a-5p, miR-26a-5p, and miR-22-3p) were loaded into EVs. The intracellular concentration of each miRNA in cells was determined. In addition, an animal study giving an oral dose of loaded EVs in C57BL6/ mice were performed. Gene expression regulation was assessed by microarray analysis. RESULTS: Digestive stability analysis showed high overall degradation of exogenous miRNAs, although EV-protected miRNAs better resisted gastrointestinal digestion compared to free miRNAs (tenfold higher levels). Importantly, orally delivered EV-loaded miRNAs reached host organs, including brain, in mice. However, no biological effect has been identified. CONCLUSION: Milk EVs protect miRNAs from degradation and facilitate cellular uptake. miRNA concentration in EVs from bovine milk might be insufficient to produce gene modulation. Nevertheless, sizable amounts of exogenous miRNAs may be loaded into EVs, and orally delivered EV-loaded miRNAs can reach tissues in vivo, increasing the possibility of exerting biological effects. Further investigation is justified as this could have an impact in the field of nutrition and health (i.e., infant formulas elaboration).

Topical Delivery of Hedgehog Inhibitors: Current Status and Perspectives.

Systemic treatment with hedgehog inhibitors (HHis) is available to treat basal cell carcinomas but their utility is limited by adverse effects. Topical delivery methods may reduce adverse effects, but successful topical treatment depends on sufficient skin uptake, biological response, and time in tumor tissue. The aim of this review was to evaluate the current status of topical HHi delivery for BCCs and discuss barriers for translating systemic HHis into topical treatments. A literature search identified 16 preclinical studies and 7 clinical trials on the topical delivery of 12 HHis that have been clinically tested on BCCs. Preclinical studies on drug uptake demonstrated that novel formulations, and delivery- and pre-treatment techniques enhanced topical HHi delivery. Murine studies showed that the topical delivery of sonidegib, itraconazole, vitamin D3 and CUR-61414 led to biological responses and tumor remission. In clinical trials, only topical patidegib and sonidegib led to at least a partial response in 26/86 BCCs and 30/34 patients, respectively. However, histological clearance was not observed in the samples analyzed. In conclusion, the incomplete clinical response could be due to poor HHi uptake, biodistribution or biological response over time. Novel topical delivery techniques may improve HHi delivery, but additional research on cutaneous pharmacokinetics and biological response is needed.

Estimation of Patient Acceptable Symptom State (PASS) and Treatment Failure (TF) Threshold Values for the Achilles Tendon Total Rupture Score (ATRS) at 6 Months, 1 Year, and 2 Years After Acute Achilles Tendon Rupture.

Interpretation of the Achilles tendon Total Rupture Score (ATRS) is challenging because limited knowledge exists about at which score the patients consider the outcome of treatment as satisfactory. The aims of the study were (1) to describe the proportion of patients who find their symptom levels to be satisfactory, to reflect treatment failure or neither after acute Achilles tendon rupture (ATR), and (2) to estimate the Patient Acceptable Symptom State (PASS) and the Treatment Failure (TF) threshold values for the ATRS at 6 months, 1 year, and 2 years after ATR. The study was based on data extracted from the nationwide Danish Achilles tendon Database which includes patients treated operatively or nonoperatively after ATR. The PASS and TF threshold values for ATRS were estimated using the adjusted predictive modeling method. One hundred and sixty-six patients were included at 6 months, 248 patients at 1 year, and 287 patients at 2 years after ATR. The proportion of patients who considered their symptom level to be satisfactory was 61% at 6 months, 50% at 1 year, and 66% at 2 years, while 5% at 6 months, 11% at 1 year, and 10% at 2 years considered their symptom level to reflect treatment failure. The PASS threshold value for ATRS (95% confidence interval) was 49 (46-52) at 6 months, 57 (54-60) at 1 year, and 52 (49-55) at 2 years. The TF threshold value for ATRS was 30 (23-36) at 6 months, 33 (26-40) at 1 year, and 35 (29-39) at 2 years. The calculated PASS and TF threshold values can help interpret the outcome of ATR when measured with the ATRS. About 50% to 66% of the patients had a satisfactory symptom level after ATR.

The Copenhagen Achilles Length Measurement Performed at Time of Acute Achilles Tendon Rupture is Correlated to Tendon Elongation After 1 Year.

Elongation of the tendon has been proposed as the most important factor leading to poor outcome after acute Achilles tendon rupture (ATR). The aim of this paper was to investigate if Amlang's ultrasound classification (AmC) or the Copenhagen Achilles Length Measurement (CALM) when assessed in the acute phase after ATR could predict elongation 1 y after rupture. 107 males and 27 females, aged 18 to 70 y and treated nonsurgically were included. AmC and CALM were assessed at time of rupture and correlated to elongation measured with CALM and Achilles Tendon Resting Angle (ATRA) at 1 y. Receiver operating characteristic (ROC) analysis was performed to determine a cut off for acceptable elongation at time of rupture given that elongation at 1 y was not to exceed 10%. AmC showed no statistically significant correlation. CALM at baseline correlated to CALM at 1 y r = 0.214 (p = .02) and ATRA at 1 y r = 0.218 (p = .02). The ROC model had AUC = 0.67 for 7% elongation at baseline yielding a sensitivity of 0.77 and specificity of 0.50 for predicting elongation of 10% or more at 1 y. Elongation of the Achilles tendon at baseline measured with CALM was weakly correlated to elongation at 1 y. A cut off of 7% elongation at baseline caught 77% of patients who, when treated nonsurgically, ended up with an elongation above 10% at 1 y. A prospective trial investigating CALM as part of a selection algorithm for deciding between operative and nonoperative treatment is needed.

Neither heel-rise Height (HRH) nor Achilles tendon resting angle (ATRA) show strong correlations to patient limitations and return to previous activities one year after acute Achilles tendon rupture.

BACKGROUND: Knowledge is limited about how Achilles tendon elongation following acute Achilles tendon rupture (ATR) affects the ability to return to work and return to sport. This study aimed to examine if the indirect length measures, the heel-rise height (HRH) and the Achilles tendon resting angle (ATRA), correlated with patient limitations and return to previous activities one year after ATR. METHODS: The study was performed as a registry study in the Danish Achilles tendon Database (DADB). The analyses investigated if HRH (limb symmetry index (LSI)) and relative ATRA one year after rupture, correlated with return to the same type of work, return to the same type of sport and the Achilles tendon total rupture score (ATRS) at the same time point. RESULTS: 477 patients were included in the study. HRH (LSI) showed fair correlation to ATRS (r = 0.35, p < 0.001), poor correlation to same type of work (r = 0.29, p < 0.001) and did not statistically significantly correlate with return to the same type of sport. Relative ATRA showed poor correlation to ATRS (r = 0.09, p = 0.04) and did not correlate statistically significantly with return to same type of work or sport. CONCLUSIONS: Neither relative ATRA nor HRH (LSI) showed strong correlations to return to work, return sport or ATRS. When comparing the relative ATRA and HRH (LSI), HRH (LSI) seems to be a better outcome in reflecting patient limitations and return to previous activities one year after ATR.

Antigen Expression Varies Significantly between Molecular Subgroups of Acute Myeloid Leukemia Patients: Clinical Applicability Is Hampered by Establishment of Relevant Cutoffs.

INTRODUCTION: In this single-center study of 268 acute myeloid leukemia (AML) patients, we have tested if a subset of 4 routinely employed immunophenotypic stem cell-associated markers correlated with the presence of recurrently mutated genes and if the markers were predictive for mutational status. METHODS: Immunophenotypic data from 268 diagnostic AML samples obtained in 2009-2018 were analyzed retrospectively for the antigens CD34, CD117, CD123, and CLEC12A. Correlation between immunophenotypes and mutations was analyzed by Fischer's exact test. Clinical applicability of the markers for predicting mutational status was evaluated by receiver operating characteristics analyses, where an area under the curve (AUC) of at least 0.85 was accepted as clinically relevant. RESULTS: For a number of genes, the antigen expression differed significantly between mutated and wild-type gene expression. Despite low AUCs, CD123 and CLEC12A correlated with FLT3+NPM1- and FLT3+NPM1+. Three subsets met the AUC requirements (CD34+, CD34+CD117+, and CD34-CD117+) for predicting FLT3-NPM1+ or FLT3+NPM1+. CONCLUSION: The value of immunophenotypes as surrogate markers for mutational status in AML seems limited when employing CD123 and CLEC12A in combination with CD34 and CD117. Defining relevant cutoffs for given markers is challenging and hampered by variation between laboratories and patient groups.

No clinically relevant difference between operative and non-operative treatment in tendon elongation measured with the Achilles tendon resting angle (ATRA) 1 year after acute Achilles tendon rupture.

PURPOSE: Studies have shown that elongation of the injured Achilles tendon after acute Achilles tendon rupture (ATR) is negatively associated with clinical outcomes. The difference between operative and non-operative treatment on the length of the Achilles tendon is only sparsely investigated. The aim of the study was to investigate if the operative and non-operative treatment of ATR had different effects on tendon elongation. METHODS: The study was performed as a registry study in the Danish Achilles tendon database (DADB). The primary outcome of the study was an indirect measure of Achilles tendon length: the Achilles tendon resting angle (ATRA) at 1-year follow-up. The variable of interest was treatment (operative or non-operative). RESULTS: From August 2015 to January 2019, 438 patients (154 operatively treated and 284 non-operatively treated) were registered with full baseline data and had their ATRA correctly registered at 1-year follow-up in DADB. The analysis did not show a clinically relevant nor statistically significant difference in ATRA between operative and non-operatively treated patients at 1-year follow-up (mean difference - 1.2°; 95% CI - 2.5; 0.1; n.s) after adjustment for potential confounders. CONCLUSION: There were neither clinically relevant nor statistically significant differences in terms of the ATRA at 1-year follow-up between the operative and non-operatively treated patients. This finding suggests that operative treatment does not lead to a clinically relevant reduction in tendon elongation compared to non-operative treatment and it should therefore not be used as an argument in the choice of treatment. LEVEL OF EVIDENCE: Level III.

Diabetes and treatment with orally administrated corticosteroids negatively affect treatment outcome at follow-up after acute Achilles tendon rupture.

PURPOSE: Studies investigating the influence of comorbidities on patient-reported outcomes after acute Achilles tendon ruptures (ATR) are lacking. In this study, the aim was to investigate the effect of comorbidity and medical treatment on the patient-reported outcome measure Achilles tendon total rupture score (ATRS). METHODS: The study was performed as a registry study from the Danish Achilles tendon Database (DADB). In the DADB, ATRS was registered at baseline (prior to rupture), at 3-6 month, 1-year and 2-year follow-ups. The outcomes were ATRS at follow-up and the change in ATRS from baseline to follow-up. Variables of interest were diabetes, hypertension, rheumatic disease and treatment with orally administrated corticosteroids. Linear mixed-effects models including all follow-up time points in the same model were used adjusting for sex, age group, treatment (operative or non-operative) and the investigated comorbidities. RESULTS: Data were collected from 2012 to 2019. Two thousand and four patients with ATR were included. Patients with the investigated comorbidities and treatment with orally administrated corticosteroid scored 10.6-19.1 points lower in mean ATRS at baseline (prior to rupture) compared to patients without the respective disease or treatment. At follow-up, patients with diabetes (mean difference, [95% CI]) (- 6.2, [- 11.7; - 0.8]; P = 0.03) and patients in treatment with orally administrated corticosteroids (- 10.9, [- 16.2; - 5.7]; P < 0.01) had a statistically significantly worse ATRS than patients without the respective disease. However, change in ATRS from baseline to follow-up was not affected. Hypertension and rheumatic disease did not affect ATRS at follow-up but had a positive effect on change in ATRS (4.3, [0.5; 8.1]; P = 0.03) and (12.0, [5.0; 19.9]; P < 0.01), respectively. No other statistically significant differences were found. CONCLUSION: This study showed that patients with diabetes, hypertension, rheumatic disease and patients in treatment with orally administrated corticosteroids had a lower ATRS at baseline (prior to the rupture) when compared to patients without the respective disease or treatment. Diabetes and treatment with orally administrated corticosteroids did negatively affect ATRS at follow-up, but none of the investigated comorbidities or treatment with orally administrated corticosteroids did negatively affect change in ATRS from baseline to follow-up. LEVEL OF EVIDENCE: Level III.

The heel-rise work test overestimates the performed work with 21-25% after an Achilles tendon rupture.

PURPOSE: The purpose of this study was to evaluate concurrent validity of the heel-rise work test performed with use of the heel as a surrogate for the center of body mass. METHODS: The study was a validity study performed on a prospective cohort of consecutive patients. Forty-five patients were included in the study. The heel-rise work test estimates the total work performed by repeated heel-rises until fatigue. In this study, the heel-rise work was assessed by the linear encoder and a motion capture system simultaneously for validation. The linear encoder was attached to the patient's heel and reflective marker was attached to the pelvis and heel. Student's paired t-test, linear regression analysis and Bland Altman plots were used to estimate the measurement error of the linear encoder. RESULTS: The heel-rise work test overestimated the total work with 21.0% on the injured leg and 24.7% on the non-injured leg. Student's paired t-test showed no difference in measurement error between the limbs (n.s.). The linear regression analysis showed no difference in limb symmetry index between the two methods of heel-rise work estimation (a (slope) = 1.00, R = 0.94, p < 0.0001). CONCLUSION: The heel-rise work test performed using the heel as a surrogate for center of body mass overestimates the total work with 21.0-24.7% compared to a gold standard but was able to precisely detect the relative difference between the limbs. The heel marker can be considered a valid measurement device for assessing relative differences between the limbs. CLINICAL RELEVANCE: Clinical testing of injuries to the lower body using the heel-rise work test is valid when using the relative difference between the limbs. LEVEL OF EVIDENCE: I.

The Achilles Tendon Length Measure and the Achilles Tendon Resting Angle show acceptable construct validity using the Copenhagen Achilles Length Measure as gold standard.

BACKGROUND: Elongation of the Achilles tendon after rupture is a frequent complication. The Achilles Tendon Length Measure (ATLM) and the Achilles Tendon Resting Angle (ATRA) are indirect length measures using the resting angle of the ankle. Copenhagen Achilles Length Measure (CALM) is a direct ultrasound measure. The purpose of this study was to examine the construct validity of ATLM and ATRA using CALM as gold standard. METHODS: As the three measurements measure slightly different constructs and have different scales a direct comparison was not possible. Instead a mixed linear regression model was performed investigating the three models: CALM-ATRA, CALMATLM and ATRA-ATLM. RESULTS: 130 patients were available for analysis. All three regression models demonstrated a statistically significant (p < 0.01) linear relationship and acceptable certainty of the estimates. CONCLUSION: ATRA and ATLM were found to have acceptable construct validity when using CALM as gold standard for assessing tendon elongation after an Achilles tendon rupture.

Efficacy of early controlled motion of the ankle compared with immobilisation in non-operative treatment of patients with an acute Achilles tendon rupture: an assessor-blinded, randomised controlled trial.

BACKGROUND: Early controlled motion (ECM) of the ankle is widely used in the non-operative treatment of acute Achilles tendon rupture, although its safety and efficacy have not been investigated properly in a randomised set-up. PURPOSE/AIM OF THE STUDY: To investigate if ECM of the ankle was superior to immobilisation in the treatment of acute Achilles tendon rupture. MATERIALS AND METHODS: This was an assessor-blinded, randomised controlled trial with patients allocated in a 1:1 ratio to one of two parallel groups. Patients aged 18-70 years were eligible for inclusion. The ECM group performed movements of the ankle five times a day from week 3 to week 8 after rupture. The control group was immobilised for 8 weeks. The primary outcome was the Achilles tendon Total Rupture Score (ATRS) evaluated at 1-year postinjury. The secondary outcomes were heel-rise work test (HRW), Achilles tendon elongation and rate of rerupture. Analysis was conducted as intention-to-treat using inverse probability weighting. FINDINGS/RESULTS: 189 patients were assessed for eligibility and 130 were included from February 2014 to December 2016. There were 64 patients in the ECM group and 58 in the immobilisation group. There were no statistically significant differences (p>0.3) between the ECM and the immobilisation groups at 1 year: mean (SD) ATRS was 74 (18) and 75 (18), respectively. HRW was 60% (21) and 60% (21) of the uninjured limb, and elongation was 18 mm (13) and 16 mm (11), respectively. Correspondingly, there were six and seven reruptures. CONCLUSIONS: ECM revealed no benefit compared with immobilisation in any of the investigated outcomes. TRIAL REGISTRATION NUMBER: NCT02015364.

Outcome after acute Achilles tendon rupture is not negatively affected by female sex and age over 65 years.

PURPOSE: Studies suggest that women have worse treatment outcome than men after acute Achilles tendon rupture (ATR). The aim of this study was to investigate if sex and age affect treatment outcome after ATR. METHODS: The study was performed as a registry study in the Danish Achilles tendon Database. The primary outcome was change in the Achilles tendon Total Rupture Score (ATRS) from baseline to 4 months, 1 year and 2 years follow-up. Variables of interest were sex and age group (< 40 years, 40-65 years and > 65 years). RESULTS: Data were collected from April 2012 to March 2018. Five-hundred and sixteen patients (416 men, 100 women) were included in the study population. At baseline, women scored 4.3 points lower in ATRS compared to men. No statistically significant difference between the sexes regarding change in ATRS were found. Women scored statistically significantly less in absolute ATRS at 1 year follow-up (mean difference 9.4; 95% CI 3.8, 14.9; P = 0.03). Patients older than 65 years scored statistically significantly more in ATRS change compared to patients between 40-65 years (mean difference 12.8; 95% CI 6.1-19.5; P < 0.001). CONCLUSION: This study did not show a statistically significant or clinically relevant difference between the sexes in ATRS change from baseline to follow-up. The mean difference in ATRS change between patients older than 65 years and patients between 40-65 years was clinically relevant with better outcome for patients older than 65 years. When comparing ATRS between groups with an unequal sex distribution, the findings of a baseline difference and a difference in absolute ATRS at 1 year follow-up between the sexes, advocate for reporting of sex-specific data or for use of change in ATRS from baseline to follow-up instead of absolute ATRS. LEVEL OF EVIDENCE: Level III.

Reliability of the Copenhagen Achilles length measure (CALM) on patients with an Achilles tendon rupture.

PURPOSE: The primary objective was to examine the reliability of the Copenhagen Achilles length measure (CALM) in patients with an Achilles tendon rupture and secondary to examine the reliability of Achilles tendon resting angle (ATRA) and Achilles tendon length measure (ATLM). METHOD: The study was executed as a cross-sectional study on two different groups: one focused on CALM and the other on ATRA/ATLM. CALM was performed on 56 patients at four timepoints during the first year after injury, whereas ATRA/ATLM were carried out on 28 patients. Intra- and inter-rater reliabilities were determined using the intra-class correlation coefficient (ICC), the standard error of the measurement (SEM), and the minimal detectable change (MDC). RESULTS: For CALM, all measurements, both for injured and non-injured sides as well as for elongation, indicated excellent relative reliability (ICC ≥ 0.75). During the four timepoints, the inter-rater absolute reliability had an SEM that ranged between 0.3 and 0.8 cm (1-4 SEM%) for injured and non-injured sides and 0.3-0.6 cm (18-29 SEM%) for elongation. On an individual level, the inter-rater absolute reliability had an MDC ranging between 0.8 and 2.2 cm (4-11 MDC%) for injured and non-injured sides and 0.8-1.7 cm (47-81 MDC%) for elongation. In the case of ATRA, relative reliability was excellent (ICC ≥ 0.75), and for ATLM, it was fair to excellent (ICC 0.58-0.79). ATRA presented a lower measurement error than ATLM. CONCLUSION: Copenhagen Achilles length measure showed excellent relative reliability, but had a significant measurement error at four timepoints the first year following an Achilles tendon rupture. LEVEL OF EVIDENCE: II.

The effect of enzymatically treated ripe banana flour on the sensory quality and glycemic response of banana-wheat flour composite muffins.

Banana are the most consumed fruit worldwide, due to their good flavour and nutritional characteristics; however, when the banana is very or over ripe, the acceptability by the consumer decreases, and in many cases the fruit must be discarded. An alternative to consume these fruits and revalue these discards is their use as a food ingredient. The presence of bioactive compounds gives added value to this type of ingredients; therefore, using methods, such as enzymatic treatment, that increase their presence is of great interest. In this work a commercial pectinase (Viscozyme L) was applied in a flour produced from whole overripe banana; then, the treated flour was used to elaborate a baked product. The aim of this work was to evaluate the effect of the incorporation of an enzymatic treated overripe banana (Musa cavendishii) flour in the sensory evaluation of muffins and, to stablish if the consumption of this food produce an effect on glycaemic response against a control food. The enzyme application produces an increment of 52% of antioxidant activity with a value of 12,791.6 µmolTE/100 g, and a presence of 4.5% RS instead 3.5% in non-treated flour. The sensory evaluation study was conducted with 4 products, using an untrained panel; selecting a muffin with 50% of wheat flour replaced with the banana treated one. This one contains 9.49% of dietary fibre. The glycaemic response study was conducted with 20 healthy volunteers, using as control a 100% wheat flour product, non-observing significant differences between both products. This work contributes to the knowledge about the potential use of a food discard as an ingredient of a food of massive consumption.

Inflammatory biomarkers in patients in Simvastatin treatment: No effect of co-enzyme Q10 supplementation.

PURPOSE: Atherosclerosis is a major risk factor for cardiovascular disease (CVD) and is known to be an inflammatory process. Statin therapy decreases both cholesterol and inflammation and is used in primary and secondary prevention of CVD. However, a statin induced decrease of plasma concentrations of the antioxidant coenzyme Q10 (CoQ10), may prevent the patients from reaching their optimal anti-inflammatory potential. Here, we studied the anti-inflammatory effect of Simvastatin therapy and CoQ10 supplementation. METHODS: 35 patients in primary prevention with Simvastatin (40 mg/day) were randomized to receive oral CoQ10 supplementation (400 mg/d) or placebo for 8 weeks. 20 patients with hypercholesterolemia who received no cholesterol-lowering treatment was a control group. Plasma concentrations of lipids and inflammatory biomarkers (interleukin-6 (IL6); -8 (IL8); -10 (IL10), tumor necrosis factor-α (TNFα); high-sensitivity C reactive protein (hsCRP)) as well as glycated hemoglobin (HbA1c) were quantified before and after the intervention. RESULTS: No significant change in inflammatory markers or lipids was observed after CoQ10 supplementation Patients in Simvastatin therapy had significantly (P < 0.05) lower baseline concentration of IL6 (0.31 ±â€¯0.03 pg/ml), IL8 (1.6 ±â€¯0.1 pg/ml) IL10 (0.16 ±â€¯0.02 pg/ml) and borderline (P = 0.053) lower TNFα (0.88 ±â€¯0.05 pg/ml), but not hsCRP (1.34 ±â€¯0.19 mg/l) compared with the control group (0.62 ±â€¯0.08, 2.6 ±â€¯0.2, 0.25 ±â€¯0.01, 1.07 ±â€¯0.09, and 1.90 ±â€¯0.35, respectively). CONCLUSIONS: Simvastatin therapy has beneficial effects on inflammatory markers in plasma, but CoQ10 supplementation seems to have no additional potentiating effect in patients in primary prevention. In contrast, glucose homeostasis may improve with CoQ10 supplementation.