Dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies in rheumatic and musculoskeletal diseases patients with COVID-19.

OBJECTIVES: Rheumatic and musculoskeletal diseases (RMD) may exhibit different immune responses to novel coronavirus (COVID-19) infection compared to healthy individuals. While previous studies have primarily investigated changes in COVID-19-related antibodies post-vaccination for RMD patients, this study sought to explore the dynamics of SARS-CoV-2 IgG antibodies and neutralising antibodies (NAb) in RMD patients after COVID-19 infection. METHODS: In this longitudinal study, we monitored the SARS-CoV-2 IgG antibodies and NAb levels in RMD patients and healthy controls (HC) at 60 and 90 days post-COVID-19 infection. Chemiluminescent immunoassay was used to detect the levels of novel coronavirus-specific IgG (anti-S1/S2 IgG) antibodies and NAb. RESULTS: A total of 292 RMD patients and 104 HC were enrolled in the study. At both the 60-day and 90-day post-COVID-19 infection, RMD patients exhibited significantly lower levels of anti-S1/S2 IgG and NAb than those in the HC group (p<0.001). The anti-S1/S2 IgG antibody levels remained relatively stable, while the NAb levels in RMD patients could vary greatly between the 60th and 90th days. A logistic regression analysis revealed that the prior administration of glucocorticoids (GC), immunosuppressants, and b/tsDMARDs stood out as independent risk factors associated with reduced anti-S1/S2 IgG and NAb levels, irrespective of the specific RMD subtypes. CONCLUSIONS: GC and anti-rheumatic medications can potentially alter the production of specific antibodies, especially NAb, in RMD patients post-COVID-19 infection. These findings emphasise the importance of continuous monitoring for NAb fluctuations in RMD patients following a COVID-19 infection.

Assessment of serum CK-MM level as a bioindicator for work-related musculoskeletal injuries among Emergency hospital workers.

Musculoskeletal disorders (MSDs) are considered a growing problem among healthcare personnel, especially service workers. The emergency room (ER) service workers are highly exposed to work-related risk factors which predispose them to MSDs. A cross-sectional study was performed on 78 ER workers. Full medical and occupational histories were taken. The Standardized Nordic Questionnaire (SNQ) was used for the assessment of musculoskeletal symptoms. Clinical examination was done with special emphasis on the locomotors system, and serum levels of muscle enzymes, including creatine kinase (CK) and creatine kinase isoenzyme (CK-MM), were measured. The study aims to detect the prevalence of occupational musculoskeletal disorders (MSDs) among ER workers at University hospitals, and assessment of CK-MM as a biomarker used in the early detection of MSDs. We found that 71.8% of the participants were complaining of musculoskeletal disorder in the last 7 days before the study, while only 34.6% were complaining of musculoskeletal disorder in the last 12 months before the study. The knee joint was the most commonly affected site in the past 7 days, by 39.7%. On the other hand, the highest prevalent disorder in the last 12 months was for the ankle joint (17.9%) with significantly high levels of serum CK-MM. In conclusion, musculoskeletal injuries are a common complaint among healthcare occupations, especially among ER service workers that need regular health education and ergonomic training programs. Monitoring of serum CK-MM level with cut-off value 90 ng\ml could be used as a novel approach for the early detection of work-related musculoskeletal disorders.

Relationship of musculoskeletal diseases with microvascular and macrovascular complications in patients with diabetes in Iran.

BACKGROUND AND AIMS: Musculoskeletal manifestations (carpal tunnel syndrome, Dupuytren's contracture, etc.) may occur in poorly controlled and longstanding diabetes. In this study, we evaluated the relationship of musculoskeletal diseases with microvascular and macrovascular complicationsin patients with diabetes. METHODS: A total of 600 patients with diabetes were enrolled in this cross-sectional study. Demographic data and historical records of the patients were retrieved. Musculoskeletal diseases were assessed by clinical examinations and then confirmed by a rheumatologist. RESULTS: Out of the 600 patients with diabetes, 61.5% (369/600) were female and 38.5% (231/600) were male. Diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy, CVA, and diabetes related ischemic heart disease were rated as 43.1%, 33.2%, 7.8%, 7.5%, and 39.6%, respectively. Significant gender differences were observed in the rates of diabetic nephropathy [56.28% for women and 43.71% for men (p value < 0.000)], diabetic peripheral neuropathy [72.34% for women and 27.65% for men (p value < 0.002)], and ischemic heart disease [57.98% for women and 42.01% for men(p value < 0.001)]. CONCLUSION: Musculoskeletal diseases usually occur in patients with poorly controlled and long-term diabetes. Due to the clear association of microvascular complications with musculoskeletal disease, more attention should be paid to the early detection of these complications in patients with diabetes.

Pathogenesis of Musculoskeletal Deficits in Children and Adults with Inflammatory Bowel Disease.

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.

Prevalence of work-related musculoskeletal disorders among Egyptian printing workers evidenced by using serum biomarkers of inflammation, oxidative stress, muscle injury, and collagen type I turnover.

OBJECTIVE: Printing workers experience a high rate of musculoskeletal disorders (MSDs). This study aims to determine the prevalence of MSDs, estimate serum biomarkers denoting musculoskeletal tissue changes, and determine some individual risk factors for MSDs among Egyptian printing workers. METHODS: Eighty-five male printing workers and 90 male administrative employees (control group) were recruited from a printing press in Giza. A validated version of the standardized Nordic questionnaire was used. Serum biomarkers of inflammation (interleukin (IL)-1α, IL-1ß, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)), cell stress or injury (malondialdehyde (MDA) and creatine kinase skeletal muscle (CK-MM)), and collagen metabolism (collagen-I carboxy-terminal propeptide (PICP) and type-I collagen cross-linked C-telopeptide (CTx)) were measured for all participants. RESULTS: This study showed a significant (p < 0.001) prevalence of the musculoskeletal symptoms (76.5%) and significant (p < 0.001) elevation in the levels of all measured biomarkers among the printing workers (means ± SD: IL-1α = 1.55 ± 0.9, IL-1ß = 1.53 ± 0.87, IL-6 = 1.55 ± 0.85, TNF-α = 4.9 ± 2.25, CRP = 6.78 ± 3.07, MDA = 3.41 ± 1.29, CK-MM = 132.47 ± 69.01, PICP = 103.48 ± 36.44, and CTx = 0.47 ± 0.16) when compared with their controls (prevalence: 34.4%; means ± SD: IL-1α = 0.88 ± 0.61, IL-1ß = 0.96 ± 0.72, IL-6 = 1.03 ± 0.75, TNF-α = 2.56 ± 1.99, CRP = 2.36 ± 1.1, MDA = 0.85 ± 0.21, CK-MM = 53.48 ± 33.05, PICP = 56.49 ± 9.05, and CTx = 0.31 ± 0.06). Also, significant (p < 0.001) positive strong associations were observed between age, body mass index (BMI), and the duration of employment with all measured biomarkers, where all correlation coefficients were >0.7. CONCLUSION: Printing workers suffer a high prevalence of work-related MSDs that might be related to some individual factors (age, BMI, and duration of employment). Consequently, preventive ergonomic interventions should be applied. Further studies should be done to elucidate the link between tissue changes and detected biomarkers to follow the initiation and progression of MSDs and study the effectiveness of curative interventions.

New Insight of Circular RNAs in Human Musculoskeletal Diseases.

Circular RNAs (circRNAs), a novel group of noncoding RNAs, are present in most eukaryotic cells. Different from messenger RNAs, circRNAs have a covalently closed single-stranded stable structure and often act in cell type and tissue-specific manners, indicating that they can be used as biomarkers. With the advance of high-throughput RNA sequencing technology and bioinformatics, a large number of circRNAs have been identified in association with musculoskeletal diseases, but the functions of most circRNAs have not been clarified. circRNAs regulate biological processes by adsorbing microRNA as "sponges," binding to proteins, acting as transcriptional regulators, and participating in translation of proteins. In this study, we discuss the latest understanding of biogenesis and gene regulatory mechanisms of circRNAs with special emphasis on new targets for musculoskeletal disease diagnosis and clinical treatment.

Nurse-managed basal-bolus versus sliding-scale insulin regimen in subjects with hyperglycemia at admission for orthopedic surgery: a propensity score approach.

AIMS: A sliding-scale (SS) regimen is discouraged to correct hyperglycemia in hospital patients, but there is resistance to adoption of basal-bolus (BB) treatment in surgical units. We tested the feasibility and the effects of a nurse-based BB regimen in orthopedic surgery. METHODS: Following an intense training to implement a protocol amenable by nurses, a group of patients admitted with hyperglycemia in an orthopedic institute were prospectively followed according to a basal-bolus insulin regimen (BB, n = 80). They were compared with a hyperglycemic group eventually treated by sliding-scale insulin on demand (SS, n = 122). Diabetes was present in 196 cases. Metabolic control was assessed during the first 3 days of surgery; outcome data were tested by logistic regression, after adjusting for propensity score. RESULT: Average blood glucose and glucose variability were lower in BB versus SS (P < 0.001), in the presence of similar 3-day insulin doses. Complications were recorded in 68 cases (16.2% vs. 45.1% in BB and SS, respectively). BB regimen was associated with propensity-adjusted reduction in all adverse events [odds ratio (OR) 0.36; 95% confidence interval (CI) 0.17-0.76] and of systemic infections (OR 0.18; 95% CI 0.07-0.50) and with shorter hospital stay (8.8 ± SD 5.2 days vs. 12.5 ± 7.4; P < 0.01). The superiority of BB regimen was confirmed in the pair-matched analysis. CONCLUSIONS: The study proves the feasibility and the superiority of nurse-based BB versus SS treatment in metabolic control and on the risk of adverse events in orthopedic surgery patients with hyperglycemia.

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. METHODS: Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF; 2 h/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. RESULTS: 10-wk HRHF rats had higher serum levels of IL-1α, IL-1ß and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1ß and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. CONCLUSIONS: Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.

The seroprevalence of Bartonella spp. in the blood of patients with musculoskeletal complaints and blood donors, Poland: a pilot study.

BACKGROUND: Bartonella spp. can cause a variety of diseases, such as lymphadenopathies, cat scratch disease, and trench fever, but can also give rise to many non-specific symptoms. No data exists regarding the prevalence of Bartonella spp. in patients with musculoskeletal complaints, nor among blood donors in Poland. METHODS: The presence of anti-Bartonella IgM and IgG in the serum of blood donors (n = 65) (Lodz, Poland) and in the patients of the Department of Rheumatology Clinic (n = 40) suffering from musculoskeletal symptoms was tested by immunofluorescence. Blood samples were cultured on enriched media. Epidemiological questionnaires were used to identify key potential risk factors, such as sex, age, contact with companion animals, and bites from insects or animals. RESULTS: Altogether, 27 of the 105 tested subjects were seropositive for Bartonella henselae IgG (23%) and three for Bartonella quintana IgG (2.85%); IgMs against B. henselae were found in three individuals (2.85%), and IgMs against B. quintana were found in one (1.54%). No statistically significant difference was found between the prevalence of B. henselae in the blood of donors or patients and the presence of unexplained musculoskeletal complaints (23% vs 30%). Individuals who had kept or been scratched by cats were not more likely to be B. henselae seropositive (p > 0.01). Tick bites were more commonly reported in patients, but insignificantly (p > 0.01). CONCLUSION: This is the first report of a high seroprevalence of anti-Bartonella IgG in patients with musculoskeletal symptoms and in blood donors in Poland. The obtained results indicate that such seroprevalence may have a possible significance in the development of musculoskeletal symptoms, although it should be confirmed on a larger group of patients. Asymptomatic bacteremia might occur and pose a threat to recipients of blood from infected donors. Hence, there is a need for more detailed research, including molecular biology methods, to clarify the potential risk of Bartonella spp. being spread to immunocompromised individuals. KEY POINTS: • This is the first study presenting high seroprevalence of Bartonella spp. in Poland. • IgG and IgM antibodies against B. quintana were found in blood samples of blood donors.

Pitfalls with Vitamin D Research in Musculoskeletal Disorders and Recommendations on How to Avoid Them

Reports suggesting that vitamin D may have extraskeletal roles have renewed interest in vitamin D research and stimulated publication of an increasing number of new studies each year. These studies typically assess vitamin D status by measuring the blood concentration of 25-hydroxyvitamin D [25(OH)D], the principal circulating metabolite of vitamin D. Unfortunately, variations in assay format, inconsistency in interpreting 25(OH)D concentrations, cohort bias (age, body mass index, race, season of measurements etc.) and failure to measure critical variables needed to interpret study results, makes interpreting results and comparing studies difficult. Further, variation in reporting results (reporting mean values vs. percent of the cohort that is deficient, no clear statement as to clinical relevance of effect size, etc.) further limits interstudy analyses. In this paper, we discuss many common pitfalls in vitamin D research. We also provide recommendations on avoiding these pitfalls and suggest guidelines to enhance consistency in reporting results.

Evidence of a distinct peripheral inflammatory profile in sport-related concussion.

BACKGROUND: Inflammation is considered a hallmark of concussion pathophysiology in experimental models, yet is understudied in human injury. Despite the growing use of blood biomarkers in concussion, inflammatory biomarkers have not been well characterized. Furthermore, it is unclear if the systemic inflammatory response to concussion differs from that of musculoskeletal injury. The purpose of this paper was to characterize systemic inflammation after injury in athletes with sport-related concussion or musculoskeletal injury. METHODS: A prospective, observational cohort study was conducted employing 175 interuniversity athletes (sport-related concussion, n = 43; musculoskeletal injury, n = 30; healthy, n = 102) from 12 sports at a sports medicine clinic at an academic institution. High-sensitivity immunoassay was used to evaluate 20 inflammatory biomarkers in the peripheral blood of athletes within 7 days of injury (subacute) and at medical clearance. Healthy athletes were sampled prior to the start of their competitive season. Partial least squares regression analyses were used to identify salient biomarker contributions to class separation between injured and healthy athletes, as well as to evaluate the relationship between biomarkers and days to recovery in injured athletes. RESULTS: In the subacute period after injury, compared to healthy athletes, athletes with sport-related concussion had higher levels of the chemokines' monocyte chemoattractant protein-4 (p < 0.001) and macrophage inflammatory protein-1ß (p = 0.001); athletes with musculoskeletal injury had higher levels of thymus and activation-regulated chemokine (p = 0.001). No significant differences in biomarker profiles were observed at medical clearance. Furthermore, concentrations of monocyte chemoattractant protein-1 (p = 0.007) and monocyte chemoattractant protein-4 (p < 0.001) at the subacute time point were positively correlated with days to recovery in athletes with sport-related concussion, while thymus and activation-regulated chemokine was (p = 0.001) positively correlated with days to recovery in athletes with musculoskeletal injury. CONCLUSION: Sport-related concussion is associated with perturbations to systemic inflammatory chemokines that differ from those observed in athletes with a musculoskeletal injury. These results support inflammation as an important facet of secondary injury after sport-related concussion that can be measured systemically in a human model of injury.

The Relationship between Plasma Levels of Interleukin-6, Multiple Organ Dysfunction and Mortality in Orthopedic Patients.

BACKGROUND: Interleukin 6 (IL-6) functions as both a pro-inflammatory cytokine and an anti-inflammatory cytokine. OBJECTIVE: To evaluate the levels of IL-6 in patients with multiple organ dysfunction syndrome (MODS). METHODS: Level of IL-6 was assessed and recorded for 14 days subsequent to the injury in 161 multiple trauma patients. MODS were diagnosed using Marshal Score. Injury Severity Scoring (ISS) was measured for all patients. RESULTS: The results of this study indicated that there was a significant relationship between the level of IL-6 and ISS on the first and second days post trauma (P=0.0001). The high level of IL-6 on the second day post trauma was associated with high mortality rate. CONCLUSION: Our study suggests the second day as the golden time for measuring the serum levels of IL-6. These findings warn us to take more health care actions in patients with higher serum levels of IL-6 on the second day.

Cabozantinib-induced serum creatine kinase elevation and musculoskeletal complaints.

Cabozantinib is a multikinase inhibitor approved for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy. While associations between serum creatine kinase (CK) elevations and other tyrosine kinase inhibitors used for the treatment of solid malignancies have been previously reported, we report a case of cabozantinib-associated CK elevation that was associated with musculoskeletal complaints by an RCC patient. Nine days following initiation of cabozantinib, the patient reported muscle cramps and serum CK had increased from levels 12 months earlier that were within normal limits to a grade 1 elevation of 244 units/L. Despite a dose reduction, her CK continued to rise over the next 2 months, leading to a peak CK of 914 units/L. Due to this grade 3 elevation, cabozantinib was permanently discontinued, and her CK subsequently returned to a grade 1 elevation within one week and then to baseline within 3 weeks. The temporal relationship between drug exposure and CK increase strongly suggests causality. To the authors' knowledge, this is the first reported case of CK elevation attributed to cabozantinib, but cabozantinib-induced CK elevations could be under-reported, and providers should monitor for musculoskeletal complaints during cabozantinib therapy.

A Prospective Study on the Effect of Corticosteroid Injection Dosage for Hand Disorders in Non-Insulin Dependent Diabetics.

Local administration of corticosteroids is an effective yet potentially dangerous intervention in the treatment of hand disorders in diabetics. Prolonged exposure to hyperglycemia contributes to non-enzymatic glycosylation of various organ systems, which may cause detrimental health effects such as blindness, renal failure, and peripheral neuropathy, contributing to the high cost of health care. The purpose of this study is to determine the effects of corticosteroid dosage on serum glucose levels when used to treat common hand disorders in diabetic patients. Twenty-one patients with non-insulin-dependent diabetes mellitus treated with a corticosteroid injection were prospectively enrolled. Either triamcinolone 10 mg (T-10 group, N = 11) or 40 mg (T-40 group, N = 10) was administered with a local anesthetic. Fasting morning serum glucose, QuickDASH scores, and visual analog scale (VAS) pain scores were recorded prior to injection. Post-prandial serum glucose was recorded the evening of the injection, and the fasting serum glucose was recorded each morning. Clinical outcomes were recorded at 6 weeks and again at an average of 26 months. Patients in both cohorts, on average, had improvements in their Quick- DASH and VAS scores after the injection without significant variation. There was a significant elevation in serum glucose in both groups. T-10 had an average glucose increase of 53 mg/dL (41%), which returned to baseline at 21 hours. T-40 had a maximum glucose increase of 50 mg/dL (40%), which returned to baseline in 58 hours. The difference in time to return to baseline was statistically significance. Both T-10 and T-40 are effective in relieving painful symptoms and improving patient functionality after injection. A lower dosage triamcinolone is associated with a quicker return of serum glucose to baseline and may be a safer alternative to higher dosages when considering prolonged hyperglycemia and its known detrimental effects of non-enzymatic glycosylation on various organ systems.

Prospective study of articular manifestations in Behçet's disease: five-year report.

AIM: To evaluate different aspects of articular involvements (prevalence, types, relation to extra-articular manifestations, etc.) in Iranian patients with Behcet's disease (BD). METHODS: In a prospective study, all patients with BD attending an outpatient BD clinic were enrolled. The type of articular involvements (peripheral or axial), involved joints, duration of attacks and their relation to extra-articular manifestations, human leukocyte antigen (HLA)-B5 and HLA-B27 were evaluated. Data analysis was done by using descriptive statistical indices such as mean and confidence interval. The comparisons were done by chi-square test. RESULTS: In a 5-year period, 2312 patients were recruited. Musculoskeletal manifestations were recorded in 430 patients (190 without previous history of these involvements). The remaining 1882 patients showed no musculoskeletal involvements, of which 753 had past histories of musculoskeletal manifestations. The 5-year incidence rate was 18.6%, and the prevalence rate was 51.2%. History of previous musculoskeletal involvements has no effect in its new development (P = 0.2). Arthritis was the most common type of involvement (289/430, 67%). The most frequent pattern was monoarthritis (191/289, 66%), and the most frequent involved joints were knees (147/289, 50.9%). The arthritic attacks were unilateral in 82.4% of cases. Ankylosing spondylitis was seen in 44/430 (10.2%). There was no association between HLA-B5 or HLA-B27 and any type of musculoskeletal involvements (P > 0.5). Pseudofolliculitis was the only extra-articular manifestation related to arthritic attacks (P = 0.046). CONCLUSION: Musculoskeletal involvement is a common manifestation of BD seen in more than half of patients. Acute knee monoarthritis was the most common pattern of articular involvement in BD.

Musculoskeletal manifestations of primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) can be associated with a variety of musculoskeletal complaints, which occasionally can be the leading or presenting manifestation. In this paper, we describe the musculoskeletal manifestations observed in patients with primary hyperparathyroidism. Medical record reviews of a select population of 74 patients with primary hyperparathyroidism are seen in a rheumatology practice. Bone manifestations included back pain in 11 patients (15.2 %), generalized bone pain in 7 patients (9.7 %), rib cage/chest pain in 6 (8.3 %), pseudoclubbing in 3, and a giant cell tumor of the mandible in 2 (2.3 %) patients. Articular manifestations such as chondrocalcinosis with or without apatite deposition disease were seen in 13 (17.7 %), arthralgias in 11 (15.2 %), and non-specific synovitis in 7 (9.7 %). Muscle weakness was observed in six patients (8.3 %) and myalgias in three (4.6 %). Less common manifestations such as Achilles tendon rupture, Jaccoud-like arthropathy, sacral insufficiency fracture, arthritis associated with fever of unknown origin (FUO), meningitis, cervical cord compression, and persistent headache were observed in single patients. Musculoskeletal findings are still a frequent and important presentation in patients with primary hyperparathyroidism seen in rheumatology practice. Some of these manifestations can be quite unusual and may represent diagnostic dilemmas to the practicing rheumatologist and/or endocrinologist.

Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study.

BACKGROUND: Farmers have an increased risk for musculoskeletal disorders (MSD) such as osteoarthritis of the hip, low back pain, and neck and upper limb complaints. The underlying mechanisms are not fully understood. Work-related exposures and inflammatory responses might be involved. Our objective was to identify plasma proteins that differentiated farmers with MSD from rural referents. METHODS: Plasma samples from 13 farmers with MSD and rural referents were included in the investigation. Gel based proteomics was used for protein analysis and proteins that differed significantly between the groups were identified by mass spectrometry. RESULTS: In total, 15 proteins differed significantly between the groups. The levels of leucine-rich alpha-2-glycoprotein, haptoglobin, complement factor B, serotransferrin, one isoform of kininogen, one isoform of alpha-1-antitrypsin, and two isoforms of hemopexin were higher in farmers with MSD than in referents. On the other hand, the levels of alpha-2-HS-glycoprotein, alpha-1B-glycoprotein, vitamin D- binding protein, apolipoprotein A1, antithrombin, one isoform of kininogen, and one isoform of alpha-1-antitrypsin were lower in farmers than in referents. Many of the identified proteins are known to be involved in inflammation. CONCLUSIONS: Farmers with MSD had altered plasma levels of protein biomarkers compared to the referents, indicating that farmers with MSD may be subject to a more systemic inflammation. It is possible that the identified differences of proteins may give clues to the biochemical changes occurring during the development and progression of MSD in farmers, and that one or several of these protein biomarkers might eventually be used to identify and prevent work-related MSD.

Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come.

The 2015 Dietary Guidelines Advisory Committee indicated that magnesium was a shortfall nutrient that was underconsumed relative to the Estimated Average Requirement (EAR) for many Americans. Approximately 50% of Americans consume less than the EAR for magnesium, and some age groups consume substantially less. A growing body of literature from animal, epidemiologic, and clinical studies has demonstrated a varied pathologic role for magnesium deficiency that includes electrolyte, neurologic, musculoskeletal, and inflammatory disorders; osteoporosis; hypertension; cardiovascular diseases; metabolic syndrome; and diabetes. Studies have also demonstrated that magnesium deficiency is associated with several chronic diseases and that a reduced risk of these diseases is observed with higher magnesium intake or supplementation. Subclinical magnesium deficiency can exist despite the presentation of a normal status as defined within the current serum magnesium reference interval of 0.75-0.95 mmol/L. This reference interval was derived from data from NHANES I (1974), which was based on the distribution of serum magnesium in a normal population rather than clinical outcomes. What is needed is an evidenced-based serum magnesium reference interval that reflects optimal health and the current food environment and population. We present herein data from an array of scientific studies to support the perspective that subclinical deficiencies in magnesium exist, that they contribute to several chronic diseases, and that adopting a revised serum magnesium reference interval would improve clinical care and public health.

Advanced Noncontrast MR Imaging in Musculoskeletal Radiology.

Multiple nonmorphologic magnetic resonance sequences are available in musculoskeletal imaging that can provide additional information to better characterize and diagnose musculoskeletal disorders and diseases. These sequences include blood-oxygen-level-dependent (BOLD), arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and diffusion-tensor imaging (DTI). BOLD and ASL provide different methods to evaluate skeletal muscle microperfusion. The BOLD signal reflects the ratio between oxyhemoglobin and deoxyhemoglobin. ASL uses selective tagging of inflowing blood spins in a specific region for calculating local perfusion. DWI and DTI provide information about the structural integrity of soft tissue including muscles and fibers as well as pathologies.

Vitamin D insufficiency in the elderly orthopaedic patient: an epidemic phenomenon.

PURPOSE: The purpose of this observational study was to evaluate serum levels of 25-OH-D of elderly patients presenting with orthopaedic illness. Furthermore, we enquired about potential confounders and risk factors of hypovitaminosis D in comorbidities and daily medication of the elderly. METHODS: Vitamin D levels in 1,083 patients aged >70 years and admitted to an orthopaedic surgery department were measured. Univariate and multivariate analyses were used to assess risk factors for insufficient vitamin D levels. RESULTS: Overall, 86 % of patients had insufficient serum levels of 25-OH-D and >60 % were vitamin D deficient. Serum vitamin D levels were lower during winter and months with fewer sunshine hours. Patients presenting with obesity, hypertension and osteoporosis were more likely to have low vitamin D levels. CONCLUSIONS: We found a high prevalence of hypovitaminosis D in elderly, nonhospitalized orthopaedic patients. Given the well-known effects of vitamin D on bone metabolism and muscle health, as well as its nonskeletal effects, vitamin D insufficiency may have a negative impact.