The Role of Skeletal Muscle Mitochondria in Colorectal Cancer Related Cachexia: Friends or Foes?

Up to 60% of colorectal cancer (CRC) patients develop cachexia. The presence of CRC related cachexia is associated with more adverse events during systemic therapy, leading to a high mortality rate. The main manifestation in CRC related cachexia is the loss of skeletal muscle mass, resulting from an imbalance between skeletal muscle protein synthesis and protein degradation. In CRC related cachexia, systemic inflammation, oxidative stress, and proteolytic systems lead to mitochondrial dysfunction, resulting in an imbalanced skeletal muscle metabolism. Mitochondria fulfill an important function in muscle maintenance. Thus, preservation of the skeletal muscle mitochondrial homeostasis may contribute to prevent the loss of muscle mass. However, it remains elusive whether mitochondria play a benign or malignant role in the development of cancer cachexia. This review summarizes current (mostly preclinical) evidence about the role of skeletal muscle mitochondria in the development of CRC related cachexia. Future human research is necessary to determine the physiological role of skeletal muscle mitochondria in the development of human CRC related cachexia.

The effect of anti-gravity training after meniscal or chondral injury in the knee. A systematic review.

Reduced impact loading or anti-gravity training has recently been introduced as a new tool in the rehabilitation of orthopaedic conditions that require restricted weight bearing. The purpose of this strategy is to speed up the functional rehabilitation while at the same time protect the healing structures from harmful effects associated with impact loading. Anti- gravity treadmills (AlterG ® ) and harness suspension devices seem to be the two most promising techniques. It is however today unclear how effective these devices are. The purpose of our study was therefore to perform a systematic literature review on the actual technology available and its effect on impact load reduction, as well as its effectiveness in accelerating functional recovery after meniscal and chondral injury to the knee. The results from our work demonstrate that only a limited number of studies are available, usually of moderate quality. The data suggest a variable effect on cartilage regeneration, and a potential for accelerated functional recovery in gait and running dynamics both with anti-gravity treadmill as well as suspension harness systems.

Feasibility, accuracy and safety of a percutaneous fine-needle biopsy technique to obtain qualitative muscle samples of the lumbar multifidus and erector spinae muscle in persons with low back pain.

The lumbar muscular system, in particular the lumbar multifidus muscle (LM) and the erector spinae muscle (ES), plays an important role in stabilizing and mobilizing the lumbar spine. Based on the topography, the lumbar paraspinal muscles can be classified into local and global muscles. LM is part of the local system, whereas ES is part of the global system. Therefore, it is interesting to investigate the muscle fibre type composition in both muscles. There is accumulating evidence that nonspecific chronic low back pain is associated with lumbar muscle dysfunction. To further elucidate this lumbar paraspinal muscle dysfunction, it is important to understand the structural characteristics of individual muscle fibres of LM and ES. Muscle fibre type composition can be investigated in muscle tissue samples. So far, muscle samples are taken by using invasive procedures that are not well tolerated. The aim of this article was to evaluate the feasibility, accuracy and safety of a percutaneous fine-needle biopsy technique to obtain muscle samples from LM and ES in persons with nonspecific chronic low back pain and to evaluate the feasibility of performing immunofluorescence analysis of myosin heavy chain isoform expression to investigate muscle fibre type composition. Preliminary investigations in cadavers were performed to determine the optimal vertebral level and puncture site to obtain muscle samples of LM and ES through a single skin puncture. In 15 persons with nonspecific chronic low back pain, muscle samples of LM and ES were taken under local anaesthesia with the percutaneous fine-needle biopsy technique, preceded by determination of the puncture site with ultrasonography. Muscle fibre type composition was investigated using immunofluorescence analysis of myosin heavy chain expression. The subjects reported little or no pain and were willing to repeat the procedure. The obtained muscle tissue contained transverse-sectioned muscle fibres in which muscle fibre contractile characteristics of the paraspinal muscles could be evaluated with immunofluorescence analysis of the myosin heavy chains. We can conclude that percutaneous microbiopsy appears to be feasible and accurate, and safe to use to obtain muscle tissue from the paraspinal muscles. The use of ultrasonography to determine the puncture site is necessary to ensure biopsy of the correct muscles and to ensure the safety of the procedure.

High intensity training improves symptoms of central sensitization at six-month follow-up in persons with chronic nonspecific low back pain: Secondary analysis of a randomized controlled trial.

BACKGROUND: High intensity training (HIT) improves disability and physical fitness in persons with chronic nonspecific low back pain (CNSLBP). However, it remains unclear if HIT affects pain processing and psychosocial factors. OBJECTIVE: To evaluate 1) the effects of HIT on symptoms of central sensitization and perceived stress and 2) the relationship of symptoms of central sensitization and perceived stress with therapy success, at six-month follow-up, in persons with CNSLBP. METHODS: This is a secondary analysis of a previously published randomized controlled trial. Persons with CNSLBP (n = 51, age=43.6y) completed the Central Sensitization Inventory (CSI) and Perceived Stress Scale (PSS) at baseline (PRE) and six months after 12-week of HIT consisting of concurrent exercise therapy (FU). Two groups were formed based on CSI scores (low-CSI/high-CSI). First, linear mixed models were fitted for each outcome, with time and groups as covariates. Multiple comparisons were executed to evaluate group (baseline), time (within-group), and interaction (between-group) effects. Second, correlation and regression analyses were performed to evaluate if baseline and changes in CSI/PSS scores were related to therapy success, operationalized as improvements on disability (Modified Oswestry Disability Index), and pain intensity (Numeric Pain Rating Scale). RESULTS: Total sample analyses showed a decrease in both CSI and PSS. Within-group analyses showed a decrease of CSI only in the high-CSI group and a decrease of PSS only in the low-CSI group. Between-group analyses showed a pronounced decrease favouring high-CSI (mean difference: 7.9; 95%CI: 2.1, 12.7) and no differences in PSS (mean difference: 0.1; 95%CI: -3.0, 3.2). CSI, but not PSS, was weakly related to therapy success. CONCLUSION: HIT improves symptoms of central sensitization in persons with CNSLBP. This effect is the largest in persons with clinically relevant baseline CSI scores. HIT also decreases perceived stress.

Observations of nemaline bodies in muscle biopsies of critically ill patients infected with SARS-CoV-2.

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1-3 and days 5-8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5-8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.

Fine-needle percutaneous muscle microbiopsy technique as a feasible tool to address histological analysis in young children with cerebral palsy and age-matched typically developing children.

Cerebral palsy (CP) is a heterogeneous group of motor disorders attributed to a non-progressive lesion in the developing brain. Knowledge on skeletal muscle properties is important to understand the impact of CP and treatment but data at the microscopic levels are limited and inconsistent. Currently, muscle biopsies are collected during surgery and are restricted to CP eligible for such treatment or they may refer to another muscle or older children in typically developing (TD) biopsies. A minimally invasive technique to collect (repeated) muscle biopsies in young CP and TD children is needed to provide insights into the early muscle microscopic alterations and their evolution in CP. This paper describes the protocol used to 1) collect microbiopsies of the medial gastrocnemius (MG) and semitendinosus (ST) in CP children and age-matched TD children, 2) handle the biopsies for histology, 3) stain the biopsies to address muscle structure (Hematoxylin & Eosin), fiber size and proportion (myosin heavy chain), counting of the satellite cells (Pax7) and capillaries (CD31). Technique feasibility and safety as well as staining feasibility and measure accuracy were evaluated. Two microbiopsies per muscle were collected in 56 CP (5.8±1.1 yr) and 32 TD (6±1.1 yr) children using ultrasound-guided percutaneous microbiopsy technique. The biopsy procedure was safe (absence of complications) and well tolerated (Score pain using Wong-Baker faces). Cross-sectionally orientated fibers were found in 86% (CP) and 92% (TD) of the biopsies with 60% (CP) and 85% (TD) containing more than 150 fibers. Fiber staining was successful in all MG biopsies but failed in 30% (CP) and 16% (TD) of the ST biopsies. Satellite cell staining was successful in 89% (CP) and 85% (TD) for MG and in 70% (CP) and 90% (TD) for ST biopsies, while capillary staining was successful in 88% (CP) and 100% (TD) of the MG and in 86% (CP) and 90% (TD) for the ST biopsies. Intraclass coefficient correlation showed reliable and reproducible measures of all outcomes. This study shows that the percutaneous microbiopsy technique is a safe and feasible tool to collect (repeated) muscle biopsies in young CP and TD children for histological analysis and it provides sufficient muscle tissue of good quality for reliable quantification.

Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.

Introduction: There is an unmet need for biomarkers to identify patients with axial spondyloarthritis (axSpA). Increasing evidence suggest the presence of autoantibodies in a subset of axSpA patients. The aim of this study was to identify novel IgA antibodies in early axSpA patients and to determine their diagnostic potential in combination with previously determined IgG antibodies against UH (Hasselt University)-axSpA-IgG antigens. Methods: An axSpA cDNA phage display library constructed from axSpA hip synovium, was used to screen for novel IgA antibodies in plasma from early axSpA patients. The presence of these antibodies against novel UH-axSpA-IgA antigens was determined in two independent axSpA cohorts, in healthy controls and in patients with chronic low back pain. Results: We identified antibodies to 7 novel UH-axSpA-IgA antigens, of which 6 correspond to non-physiological peptides and 1 to the human histone deacetylase 3 (HDAC3) protein. IgA antibodies against 2 of these 7 novel UH-axSpA-IgA antigens and IgG antibodies against 2 of the previously identified antigens were significantly more present in early axSpA patients from the UH cohort (18/70, 25.7%) and the (Bio)SPAR cohort (26/164, 15.9%), compared to controls with chronic low back pain (2/66, 3%). Antibodies to this panel of 4 antigens were present in 21.1% (30/142) of patients with early axSpA from the UH and (Bio)SPAR cohorts. The positive likelihood ratio for confirming early axSpA using antibodies to these 4 UH-axSpA antigens was 7.0. So far, no clinical correlation between the novel identified IgA antibodies and inflammatory bowel disease could be identified. Discussion: In conclusion, screening an axSpA cDNA phage display library for IgA reactivity resulted in the identification of 7 novel UH-axSpA-IgA antigens, of which 2 show promising biomarker potential for the diagnosis of a subset of axSpA patients, in combination with previously identified UH-axSpA-IgG antigens.

Efficacy of 12 weeks oral beta-alanine supplementation in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD. METHODS: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV1 % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed. RESULTS: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO2 peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes. CONCLUSIONS: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed.

Certainty-Based Marking on Multiple-Choice Items: Psychometrics Meets Decision Theory.

When a response to a multiple-choice item consists of selecting a single-best answer, it is not possible for examiners to differentiate between a response that is a product of knowledge and one that is largely a product of uncertainty. Certainty-based marking (CBM) is one testing format that requires examinees to express their degree of certainty on the response option they have selected, leading to an item score that depends both on the correctness of an answer and the certainty expressed. The expected score is maximized if examinees truthfully report their level of certainty. However, prospect theory states that people do not always make rational choices of the optimal outcome due to varying risk attitudes. By integrating a psychometric model and a decision-making perspective, the present study looks into the response behaviors of 334 first-year students of physiotherapy on six multiple-choice examinations with CBM in a case study. We used item response theory to model the objective probability of students giving a correct response to an item, and cumulative prospect theory to estimate their risk attitudes when students choose to report their certainty. The results showed that with the given CBM scoring matrix, students' choices of a certainty level were affected by their risk attitudes. Students were generally risk averse and loss averse when they had a high success probability on an item, leading to an under-reporting of their certainty. Meanwhile, they were risk seeking in case of small success probabilities on the items, resulting in the over-reporting of certainty.

Unilateral changes of the multifidus in persons with lumbar disc herniation: a systematic review and meta-analysis.

BACKGROUND: Lumbar disc herniation (LDH) is one of the most often diagnosed degenerative pathologies within the lumbar spine. Paraspinal muscle involvement could be a possible mediator in the pathophysiology of disc herniation and influences the course of pain and disability after both surgical or nonsurgical treatment. To potentially improve treatment, it may be important to assess multifidus muscle morphology in patients diagnosed with a LDH. OBJECTIVE: A systematic literature review and meta-analysis regarding the multifidus morphology in patients diagnosed with a LDH was conducted to assess the differences in multifidus muscle morphology between persons with LDH and healthy controls, and between the involved and the uninvolved side within subjects experiencing unilateral LDH. METHODS: A systematic search was conducted of articles published up to and including November 2019 using the Pubmed, Web of Science, EMBASE, and MEDLINE Ovid search engines. The articles obtained from this search were screened based on title and abstract using the predetermined eligibility criteria. Included full text articles were assessed for their methodologic quality using the modified Downs and Black checklist. Heterogeneous data regarding multifidus muscle morphology was included in the descriptive analysis; data that was homogenous was included in the meta-analysis. RESULTS: We identified 3,176 articles. Based on the screening for inclusion/exclusion criteria, 18 articles were included. Studies were either cross sectional or case-control studies assessing side-to-side differences or comparing patients diagnosed with a LDH to a healthy control group. Nine studies investigated whole muscle atrophy, six looked at muscle fat infiltration, seven studies assessed microscopic muscle properties including muscle fiber size, distribution, and muscle fibrosis. From the 18 articles, 10 were included in the meta-analysis. In the meta-analysis, a comparison was made between side-to-side differences for muscle fiber size, distribution, and whole muscle size. Descriptive analysis showed increased fat infiltration and atrophy (muscle and individual fiber) of the multifidus muscle when comparing side-to-side differences or comparing cases to controls. Meta-analysis showed a significant decrease in type I and II muscle fiber size (p=.002, .01, respectively) combined with a significant increase in the number of type I muscle fibers (p=.008) at the side of LDH. Regarding whole muscle size, no significant differences were found. CONCLUSIONS: This study shows the presence of ipsilateral multifidus muscle changes in persons with unilateral LDH.

Biopsy samples from the erector spinae of persons with nonspecific chronic low back pain display a decrease in glycolytic muscle fibers.

BACKGROUND CONTEXT: Low back pain (LBP) in Western Europe was classified as having the highest disability and overall burden among 291 studied conditions. For an extensive period of time, evidence related to morphological changes (eg, atrophy and fat infiltration) of the paraspinal muscles in persons with LBP has accumulated. Despite this evidence, there is limited knowledge on muscle fiber type composition of these muscles, and their relation to LBP. PURPOSE: The aim of the study is to investigate differences in muscle fiber type composition between persons with nonspecific chronic low back pain (NSCLBP) and healthy controls for the lumbar erector spinae (ES) and multifidus (MF) muscle. STUDY DESIGN AND SETTING: A cross-sectional study took place in the REVAL Rehabilitation Research Center, Hasselt University, Diepenbeek, Belgium. PATIENT SAMPLE: Twenty persons with NSCLBP (age: 44.5±7.42) and 18 healthy controls (age: 39.89±7.90) participated in this study. OUTCOME MEASURES: The primary outcome measure was paraspinal muscle fiber type composition. Secondary outcomes consisted of physiologic measures (maximal aerobic capacity and back muscle strength) and functional measures (activity level). METHODS: Biopsy samples were taken from the lumbar ES and MF muscle at the L4 spinal level. These samples were stained using immunofluorescent antibodies against myosin heavy chains. In each sample, number and size (CSA) of type I, I/IIa, IIa, IIa/x, and IIx muscle fibers were quantified. From these data the relative cross-sectional fiber areas (RCSA) were calculated. To analyze differences in fiber type composition between healthy persons and persons with NSCLBP, a repeated measurements analysis of variance was used. Secondary outcome measures were analyzed using a Student's t test, and Wilcoxon test. This study was supported by the research fund of Hasselt University without potential conflict of interest. RESULTS: There were no significant differences between both groups regarding anthropometric data. There were no significant between group differences for CSA in the ES. Persons with NSCLBP displayed a nonsignificant (p=.0978) increase in the number of type I muscle fibers, and a significant decrease (p=.0019) in the number of type IIx muscle fibers in the ES muscle. Persons with NSCLBP also displayed a trend toward a higher (p=.0596) RCSA for type I fibers and a significantly lower RCSA for type IIx fibers (p=.0411). There were no significant between group differences within the MF. Regarding the secondary outcome measures, there was a significant between group difference in activity level (p=.0004) and isokinetic back muscle strength (p=.0342). CONCLUSIONS: This is the first study to examine muscle fiber type characteristics in both the ES and MF muscle of persons with NSCLBP. Based on muscle fiber characteristics, the paraspinal muscles of persons with NSCLBP seems to display a larger oxidative potential based on an increase of the number type I fibers at the expense of type IIx glycolytic fibers.

Gluteus Maximus Transfer as an Augmentation Technique for Patients With Severe Abductor Deficiency of the Hip.

Impaired abductor function of the hip following severe abductor deficiencies can be devastating for functionality and quality of life. Recently, gluteus maximus transfer has been proposed as a solution to these difficult problems. However, outcome results are sparse. The aim of this study was to evaluate the effects of gluteus maximus transfer on improvement of pain, disability, and quality of life in patients with severe hip abductor deficiencies. Gluteus maximus transfer was performed in 16 patients with severe disruption of the abductor muscles of the hip. Data were collected preoperatively and at 6 weeks, 3 and 6 months, and 1 to 2 years after surgery. The measurements pertained to complications, healing of the flap based on magnetic resonance imaging (MRI) findings (in 10 patients), evaluation of Trendelenburg gait and sign, and patient-reported outcome measures of pain, disability, and quality of life. Preoperatively, all patients had a positive Trendelenburg sign and reported severe pain at the level of the greater trochanter. At a mean follow-up of 20 months, the Trendelenburg sign was negative in 7 patients and the Trendelenburg gait had disappeared in 7 patients. There was an improvement in patient-reported outcome measures but not to a significant level except for the pain subscores. Two patients had a postoperative seroma that resulted in a visible bump on the lateral side. Seven of 10 repairs with MRI follow-up showed perfect ingrowth on MRI without signs of rerupture. Gluteus maximus transfer for abductor deficiency of the hip may be effective for pain relief and functional improvements. Most patients showed an improved quality of life but were not completely pain free. [Orthopedics. 2020;43(4):e299-e305.].

Extra-Articular Impingement at the Anterior Inferior Iliac Spine: A Cause of Refractory Periarticular Pain After Total Hip Arthroplasty.

BACKGROUND: Periarticular pain after total hip arthroplasty (THA) can significantly impair the postoperative functionality. Extra-articular impingement between the greater trochanter and the anterior inferior iliac spine is presented as a cause of refractive pain after THA. METHODS: Twenty patients were treated for refractive periarticular pain and limited internal rotation between January 2014 and April 2016. All patients underwent a positive chair rise test, pelvic inclination test, and Marcainisation test. Patients were treated with bone resection of the anterior part of the greater trochanter with or without component revision. RESULTS: At a mean follow-up of 20 months, all functional outcomes had improved significantly. All patients were willing to undergo the surgery again. Sixteen (80%) indicated the result as very good, 3 (15%) as good, and one (5%) as poor. Two patients developed a postoperative heterotopic ossification that required resection. CONCLUSIONS: Extra-articular impingement should be considered as a possible cause of refractive groin pain after THA. Bony resection through the Hueter interval provides immediate pain relief with improved functional outcomes 1 year after surgery.

The lumbar multifidus is characterised by larger type I muscle fibres compared to the erector spinae.

The metabolic capacity of a muscle is one of the determinants of muscle function. Muscle fiber type characteristics give an indication about this metabolic capacity. Therefore it might be expected that the lumbar multifidus (MF) as a local stabilizer contains higher proportions of slow type I fibers, compared to the erector spinae (ES) as a global mobilizer. The aim of this study is to determine the muscle fiber characteristics of the ES and MF to provide insight into their structural and metabolic characteristics, and thereby the functional capacity of both muscles. Muscle fiber type characteristics in the ES and MF were investigated with an immunofluorescence staining of the myosin heavy chain isoforms. In both the ES and MF, type I muscle fibers are predominantly present. The cross-sectional area (CSA) of type I muscle fibers is significantly larger in the lumbar MF compared to the ES. However, the mean muscle fiber type percentage for type I was not significantly different, which resulted in an insignificant difference in relative cross-sectional area (RCSA) for type I. No significant differences were found for all other muscle fiber types. This may indicate that the MF displays muscle fiber type characteristics that tend to be more appropriate to maintain stability of the spine. However, because we could not demonstrate significant differences in RCSA between ES and MF, we cannot firmly state that there are functional differences between the ES an MF based only on structural characteristics.

Disability, kinesiophobia, perceived stress, and pain are not associated with trunk muscle strength or aerobic capacity in chronic nonspecific low back pain.

OBJECTIVES: To investigate to which extent disability, psychological and pain-related factors are associated with the outcomes of an isometric trunk muscle strength test and a cardiopulmonary exercise test in persons with chronic nonspecific low back pain (CNSLBP). DESIGN: Cross-sectional study. SETTING: REVAL Rehabilitation Research Center (Hasselt, Belgium). PARTICIPANTS: Persons with CNSLBP. MAIN OUTCOME MEASURES: Questionnaires concerning disability, patient specific functioning, kinesiophobia, perceived stress, pain intensity, and central sensitization were recorded. Outcomes of an isometric trunk strength test (maximum back and abdominal torque) and cardiopulmonary exercise test (VO2max) were assessed. Multivariate linear regression models determined factors explaining outcome variance. RESULTS: Data of 101 persons (39 males, mean age: 44.2y (SD = 9.6)) was assessed. Neither disability, nor psychological, nor pain-related factors were associated with the assessments. Variance in back muscle strength (R2 = 0.44, F = p < 0.01), abdominal muscle strength (R2 = 0.68, F = p < 0.01), and aerobic capacity (R2 = 0.76, F = p < 0.01) could only be explained through the included demographics covariates (age, gender, weight). CONCLUSION: This study highlighted the lack of biopsychosocial factors in explaining variance in outcomes of abdominal and back strength, and aerobic capacity in persons with CNSLBP with characteristics as depicted in the current sample. This information supports the valid interpretation of the outcomes of these assessments.

High Intensity Training to Treat Chronic Nonspecific Low Back Pain: Effectiveness of Various Exercise Modes.

High-intensity training (HIT) improves rehabilitation outcomes such as functional disability and physical performance in several chronic disorders. Promising results were also found in chronic nonspecific low back pain (CNSLBP). However, the impact of different exercise modes on HIT effectiveness in CNSLBP remains unclear. Therefore, this study evaluated the effectiveness of various HIT exercise modes and compared differences between these modes, on pain intensity, disability, and physical performance, as a therapeutic intervention for persons with CNSLBP. In a randomized comparative trial, consisting of a 12-week program, persons with CNSLBP were divided into four HIT groups, i.e., cardiorespiratory interval training coupled with either general resistance training, core strength training, combined general resistance and core strength training, or mobility exercises. Before and after the program, the Numeric Pain Rating Scale (NPRS), Modified Oswestry Disability Index (MODI), and Patient Specific Functioning Scale (PSFS) were recorded, and a cardiopulmonary exercise test (VO2max, cycling time) and isometric trunk strength test (maximum muscle torque) were performed. Eighty participants (mean age: 44.0 y, 34 males) were included. Improvements were found within all groups after the HIT programs and ranged from -39 to -57% on the NPRS, +27 to +64% on the MODI, +38 to +89% on the PSFS, +7 to +14% on VO2max, and +11 to +18% on cycling time. No differences between groups were found. High-intensity cardiorespiratory interval training improves CNSLBP rehabilitation outcomes when performed with other HIT exercise modes or mobility exercises. Hence, when setting up an exercise therapy program in CNSLBP rehabilitation, various HIT modes can be considered as therapy modalities.

Impact of Exercise-Nutritional State Interactions in Patients with Type 2 Diabetes.

INTRODUCTION: This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. METHODS: Twenty-five male patients (glycated hemoglobin (HbA1c), 57 ± 3 mmol·mol (7.4% ± 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. RESULTS: Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (-1.6 kg) and increased high-density lipoprotein concentrations (+2 mg·dL), physical fitness (+1.7 mL·min·kg), and fat oxidation during exercise in both groups (PTIME < 0.05), with no between-group differences (PTIME × GROUP > 0.05). HbA1c concentrations significantly decreased after exercise training (PTIME < 0.001), with a significant greater reduction after consuming breakfast (-0.30% ± 0.06%) compared with fasted state (-0.08% ± 0.06%; mean difference, 0.21%; PTIME × GROUP = 0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. CONCLUSIONS: Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1c seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state.

Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts.

OBJECTIVE: This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. METHODS: An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. RESULTS: We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. CONCLUSION: Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.

Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane.

We have demonstrated previously that adult human synovial membrane-derived mesenchymal stem cells (hSM-MSCs) have myogenic potential in vitro (De Bari, C., F. Dell'Accio, P. Tylzanowski, and F.P. Luyten. 2001. Arthritis Rheum. 44:1928-1942). In the present study, we have characterized their myogenic differentiation in a nude mouse model of skeletal muscle regeneration and provide proof of principle of their potential use for muscle repair in the mdx mouse model of Duchenne muscular dystrophy. When implanted into regenerating nude mouse muscle, hSM-MSCs contributed to myofibers and to long term persisting functional satellite cells. No nuclear fusion hybrids were observed between donor human cells and host mouse muscle cells. Myogenic differentiation proceeded through a molecular cascade resembling embryonic muscle development. Differentiation was sensitive to environmental cues, since hSM-MSCs injected into the bloodstream engrafted in several tissues, but acquired the muscle phenotype only within skeletal muscle. When administered into dystrophic muscles of immunosuppressed mdx mice, hSM-MSCs restored sarcolemmal expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor.

General practitioners' predictions of their own patients' health literacy: a cross-sectional study in Belgium.

OBJECTIVES: To support patients in their disease management, providing information that is adjusted to patients' knowledge and ability to process health information (ie, health literacy) is crucial. To ensure effective health communication, general practitioners (GPs) should be able to identify people with limited health literacy. To this end, (dis)agreement between patients' health literacy and GPs' estimations thereof was examined. Also, characteristics impacting health literacy (dis)agreement were studied. DESIGN: Cross-sectional survey of general practice patients and GPs undertaken in 2016-17. SETTING: Forty-one general practices in two Dutch-speaking provinces in Belgium. PARTICIPANTS: Patients (18 years of age and older) visiting general practices. Patients were excluded when having severe impairments (physical, mental, sensory). MAIN OUTCOME MEASURES: Patients' health literacy was assessed with 16-item European Health Literacy Survey Questionnaire. GPs indicated estimations on patients' health literacy using a simple scale (inadequate; problematic; adequate). (Dis)agreement between patients' health literacy and GPs' estimations thereof (GPs' estimations being equal to/higher/lower than patients' health literacy) was measured using Kappa statistics. The impact of patient and GP characteristics, including duration of GP-patient relationships, on this (dis)agreement was examined using generalised linear logit model. RESULTS: Health literacy of patients (n=1375) was inadequate (n=201; 14.6%), problematic (n=299; 21.7%), adequate (n=875; 63.6%). GPs overestimated the proportion patients with adequate health literacy: adequate (n=1241; 90.3%), problematic (n=130; 9.5%) and inadequate (n=4; 0.3%). Overall, GPs' correct; over-/underestimations of health literacy occurred for, respectively, 60.9%; 34.2%; 4.9% patients, resulting in a slight agreement (κ=0.033). The likelihood for GPs to over-/underestimate patients' health literacy increases with decreasing educational level of patients; and decreasing number of years patients have been consulting with their GP. CONCLUSIONS: Intuitively assessing health literacy is difficult. Patients' education, the duration of GP-patient relationships and GPs' gender impact GPs' perceptions of patients' health literacy.