Local steroid injection for moderately severe idiopathic carpal tunnel syndrome: Protocol of a randomized double-blind placebo-controlled trial (NCT 00806871)

<p>Abstract</p> <p>Background</p> <p>Patients with idiopathic carpal tunnel syndrome (CTS) are commonly treated with steroid injection into or proximal to the carpal tunnel. However, evidence for its efficacy beyond one month has not been established in randomized placebo-controlled trials. The primary aim of this randomized trial is to assess the efficacy of steroid injection into the carpal tunnel in relieving symptoms of CTS in patients with symptoms of such severity to warrant surgical treatment but have not been treated with steroid injection.</p> <p>Methods/Design</p> <p>The study is a randomized double-blind placebo-controlled trial. Patients referred to one orthopedic department because of CTS are screened. Eligibility criteria are age 18 to 70 years, clinical diagnosis of primary idiopathic CTS and abnormal nerve conduction tests or clinical diagnosis made independently by two orthopedic surgeons, failed treatment with wrist splinting, symptom severity of such magnitude that the patient is willing to undergo surgery, no severe sensory loss or thenar muscle atrophy, and no previous steroid injection for CTS. A total of 120 patients will be randomized to injection of 80 mg Methylprednisolone, 40 mg Methylprednisolone, or normal saline, each also containing 10 mg Lidocaine. Evaluation at baseline and at 5, 10, 24 and 52 weeks after injection includes validated questionnaires (CTS symptom severity scale, <it>Quick</it>DASH and SF-6D), adverse events, physical examination by a blinded assessor, and nerve conduction tests. The primary outcome measures are change in the CTS symptom severity score at 10 weeks and the rate of surgery at 52 weeks. The secondary outcome measures are the score change in the CTS symptom severity scale at 52 weeks, time to surgery, and change in <it>Quick</it>DASH and SF-6D scores and patient satisfaction at 10 and 52 weeks. The primary analysis will be carried out using mixed model analysis of repeated measures.</p> <p>Discussion</p> <p>This paper describes the rationale and design of a double-blind, randomized placebo-controlled trial that aims to determine the efficacy of two different doses of steroid injected into the carpal tunnel in patients with moderately severe idiopathic CTS.</p> <p>Trial registration</p> <p>Clinicaltrials.gov identifier NCT00806871</p

Interleukin-6 receptor pathways in abdominal aortic aneurysm

We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach

Carpal tunnel syndrome. Diagnosis and treatment.

Carpal Tunnel Syndrome (CTS) is the most common compression neuropathy causing pain, impaired hand function and sick leave. CTS is usually diagnosed based on patient history and clinical tests. In some patients an additional ENeG is done to support the diagnosis. However, ENeG can show pathology in healthy people and show normal values in patients with overwhelming clinical signs of CTS. Traditionally CTS is treated with CTR, however it is well known that a number of patients do not improve after surgery. The understanding of the human nervous system has increased dramatically during the last few decades. This has made it possible to better understand symptoms seen in patients with nerve injuries and to design treatment strategies where the dynamic capacity of the brain, i.e. brain plasticity is guided for therapeutic purposes. The aim of this thesis was to assess cerebral changes following CTS, and evaluate treatment using guided plasticity for patients with CTS. A further aim was to evaluate whether analysis of vibration perception thresholds at multiple frequencies can detect CTS, and if ENeG results are important for post-operative outcome following CTR.The first two studies evaluated the clinical and cerebral effects of treatment using guided plasticity in the form of cutaneous forearm anesthesia over 8 weeks. The results show that cutaneous stimulation of the hand with CTS causes activation of fewer neurons in the S1 compared to stimulation of a healthy hand. The concept of guided plasticity works, and treatment using guided plasticity results in recruitment of more neurons in the S1. However, it does not result in improved sensory function in the affected hand. Study III shows that patients with clinical and ENeG-verified CTS have increased vibration perception thresholds at multiple frequencies in all fingers. This suggests that analysis of vibration perception thresholds using multi-frequency vibrometry can serve as a diagnostic tool for CTS. Study IV showed that the outcome after endoscopic CTR is beneficial. This study also shows that the subjective outcome after endoscopic CTR is better if the patient, in addition to a typical history and positive diagnostic tests also has an ENeG indicating CTS as compared to a normal ENeG

Circulating biomarkers in patients with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) develops in 3-6% of the population over 65 years and affects mainly men. AAA has a complex etiology involving inflammation, proteolysis, fibrinolysis and coagulation. The general aim of the present thesis was to study the associations between markers of inflammation, proteolysis, fibrinolysis and coagulation with aneurysm size and growth. In paper I associations between markers for these mechanisms and AAA size were evaluated. Patients with AAA had significantly increased levels of several markers ([endothelin] ET-1, [interleukin] IL-6, [tumour necrosis factor] TNF-α, APC-PCI) compared to age matched healthy controls. Correlations existed between aneurysm size, decreased platelet count, increased high sensitive-C-reactive protein, IL-6 and APC-PCI complex levels. In paper II effects of statin treatment were investigated, showing that patients on statins had lower levels of cholesterol, but also of homocysteine, ceruloplasmin, orosomucoid, (matrix metallo-proteinase) MMP-9 and ET-1 in plasma, but higher levels of albumin, and the APC-PCI complex. In paper III relationships between markers of proteolysis, fibrinolysis and coagulation and aneurysm size and growth during follow-up were studied. MMP-2 levels were lower in AAA patients than in healthy controls. Only MMP-2 was related to AAA size. In paper IV relationships between markers of inflammation and endothelial function and aneurysm growth were studied. We confirmed that initial aneurysm diameter is related to yearly AAA growth. Furthermore, age and initial levels of ET-1 were also related to AAA growth during 7 years follow-up. In paper V patterns of systemic biomarkers and their relationship to aneurysm growth during yearly follow-up of patients with AAA were analyzed. Few relationships were demonstrated between the development of mediators and aneurysm growth during annual analysis of this patient material, which was extended compared to the previous analyses. In conclusion, none of the above biomarkers can predict aneurysm growth or replace ultrasound surveillance

Plasma concentrations of growth arrest specific protein 6 and the soluble form of its tyrosine kinase receptor Axl as markers of large abdominal aortic aneurysms.

OBJECTIVE: The tyrosine kinase receptor Axl is expressed in the vasculature and Gas6 is the ligand. The extracellular part of Axl (sAxl) can be found in circulation. The aim of this study was to determine plasma concentrations of Gas6 and sAxl in patients with abdominal aortic aneurysms (AAA) and to evaluate if Gas6 and sAxl can be used as biomarkers. DESIGN AND METHODS: Immunoassays for sAxl and Gas6 were used to investigate plasma from AAA patients. Patients with large (n=123) or small AAA (n=122) were compared with healthy controls (n=141). RESULTS: Gas6 correlated positively and sAxl correlated negatively with AAA size. As a consequence, the calculated Gas6/sAxl ratios correlated even better to AAA size. Forty percent of all patients with a large AAA had higher Gas6/sAxl ratio than any in the control group. DISCUSSION: The Gas6/Axl system might be involved in AAA pathogenesis, and the Gas6/sAxl ratio may be useful as a biomarker

High Levels of Endothelin (ET)-1 and Aneurysm Diameter Independently Predict Growth of Stable Abdominal Aortic Aneurysms

The etiology of abdominal aortic aneurysm (AAA) includes inflammation and endothelial dysfunction. To evaluate relations between these mechanisms and AAA growth, endothelin (ET)-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and CD40 ligand were related to yearly AAA growth for 2.9 +/- 1.6 years (mean +/- SD) in 178 patients with conservatively followed AAA. Total number of follow-up years was 491. Abdominal aortic aneurysm diameter increased by 3.3 +/- 4.0 mm during the first year and by 4.9 +/- 4.4 mm during the first 2 years. Median (range) growth was 2.5 (-1.0 to 30.6) mm/year. When patients with AAA growth above or below median were compared, initial AAA diameter (46.1 +/- 5.8 vs 42.0 +/- 8.3 mm; P < .0001), age (75 +/- 7 vs 72 +/- 8 years; P < .029), and initial ET-1 levels (1.31 +/- 0.50 vs 1.13 +/- 0.49 pg/mL; P <.0177) were higher in patients with growth above median. Endothelin 1 (P = .0230) and initial AAA diameter (P = .0019) predicted AAA growth above median in logistic regression. In conclusion, higher initial levels of ET-1 and initial AAA diameter independently predict AAA growth

Invasive Mycobacterium marinum infection of the hand.

Abstract Mycobacterium marinum infection of the hand is rare. We report the case of a 39-year-old man with M marinum infection that resulted in a chronic soft tissue infection, extensor tendon synovitis, and arthritis of the metacarpophalangeal (MCP) joints. The cause was probably tropical freshwater fishes

Methylprednisolone Injections for the Carpal Tunnel Syndrome A Randomized, Placebo-Controlled Trial

Background: Steroid injections are used in idiopathic carpal tunnel syndrome (CTS), but evidence of efficacy beyond 1 month is lacking. Objective: To assess the efficacy of local methylprednisolone injections in CTS. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT00806871) Setting: Regional referral orthopedic department in Sweden. Patients: Patients aged 18 to 70 years with CTS but no previous steroid injections. Intervention: Three groups (37 patients each) received 80 mg of methylprednisolone, 40 mg of methylprednisolone, or placebo. The patients and treating surgeons were blinded. Measurements: Primary end points were the change in CTS symptom severity scores at 10 weeks (range, 1 to 5) and rate of surgery at 1 year. Three patients had missing 10-week data. All patients had 1-year data. Results: Improvement in CTS symptom severity scores at 10 weeks was greater in patients who received 80 mg of methylprednisolone and 40 mg of methylprednisolone than in those who received placebo (difference in change from baseline, -0.64 [95% CI, -1.06 to -0.21; P = 0.003] and -0.88 [CI, -1.30 to -0.46; P < 0.001], respectively), but there were no significant differences at 1 year. The 1-year rates of surgery were 73%, 81%, and 92% in the 80-mg methylprednisolone, 40-mg methylprednisolone, and placebo groups, respectively. Compared with patients who received placebo, those who received 80 mg of methylprednisolone were less likely to have surgery (odds ratio, 0.24 [CI, 0.06 to 0.95]; P = 0.042). With time to surgery incorporated, both the 80- and 40-mg methylprednisolone groups had lower likelihood of surgery (hazard ratio, 0.46 [CI, 0.27 to 0.77; P = 0.003] and 0.57 [CI, 0.35 to 0.94; P = 0.026], respectively). Limitation: The study was conducted at 1 center, and wrist splinting had previously failed for all patients. Conclusion: Methylprednisolone injections for CTS have significant benefits in relieving symptoms at 10 weeks and reducing the rate of surgery 1 year after treatment, but 3 out of 4 patients had surgery within 1 year