Efficacy of 4D-CT preoperative localization in 2 patients with MEN 2A

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome that is associated with hyperparathyroidism in 20% to 30% of adult gene carriers. The appropriate surgical management of these patients remains in question. Approaches to this disease range from selective gland resection to a subtotal parathyroidectomy with or without autotransplantation. Despite surgical intervention, disease recurrence is problematic. Surgical management of patients found to have recurrence relies on localizing the anatomic location of the hyperfunctional gland(s). The primary imaging modality for localization of hyperfunctioning parathyroid glands is technetium 99m sestamibi single photon emission computed tomography (SPECT). Although sestamibi imaging has a sensitivity of 60% to 90%, specific anatomic detail is not always present by this imaging modality. Four-dimensional computed tomography (4D-CT) scans allow localization of ectopic parathyroid glands and autotransplanted parathyroid tissue, and they provide the anatomic detail necessary for decisions about appropriate surgical management. Another benefit of the 4D-CT scan is that enhancement characteristics, which are determined by contrast opacification of the hyperfunctional parathyroid tissue over 4 phases of the scan, correlate with metabolic activity. We recommend the use of 4D-CT scanning because of its capacity to identify hyperfunctional parathyroid glands and to provide anatomic information important in preoperative planning.     

OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines

PURPOSE: To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. METHODS: Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. RESULTS: Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. CONCLUSION: Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.     

Prevalence of bone attrition on knee radiographs and MRI in a community-based cohort

OBJECTIVES: Bone attrition probably constitutes remodeling of the bone, resulting in flattening or depression of the articular surfaces. Defining bone attrition is challenging because it is an accentuation of the normal curvature of the tibial plateaus. We aimed to define bone attrition on magnetic resonance imaging (MRI) of the knee using information from both radiographs and MRIs, and to assess whether bone attrition is common prior to end stage disease osteoarthritis (OA) in the tibio-femoral joint. METHODS: All knees of participants in the community-based sample of the Framingham OA Study were evaluated for bone attrition in radiographs and MRIs. Radiographs were scored based on templates designed to outline the normal contours of the tibio-femoral joint. MRIs were analyzed using the semi-quantitative Whole-Organ Magnetic Resonance Imaging Scoring (WORMS) method. The prevalence of bone attrition was calculated using two different thresholds for MRI scores. RESULTS: Inter-observer agreement for identification of bone attrition was substantial for the radiographs (kappa=0.71, 95% CI 0.67-0.81) and moderate for MRI (kappa=0.56, 95% CI 0.40-0.72). Of 964 knees, 5.7% of the radiographs showed bone attrition. Of these, 91% of MRIs were also read as showing bone attrition. We selected a conservative threshold for bone attrition on MRI scoring (>/=2 on a 0-3 scale) based on agreement with attrition on the radiograph or when bone attrition on MRI co-occurred with cartilage loss on OA. Using this threshold for bone attrition on MRI, bone attrition was common in knees with OA. For example, in knees with mild OA but no joint space narrowing, 13 of 88 MRIs (14.8%) showed bone attrition. CONCLUSIONS: Using MRI we found that many knees with mild OA without joint narrowing on radiographs had bone attrition, even using conservative definitions. The validity of our definition of bone attrition should be evaluated in further studies. Bone attrition may occur in milder OA and at earlier stages of disease than previously thought.     

Parathyroid exploration in the reoperative neck: improved preoperative localization with 4D-computed tomography

BACKGROUND: Reoperation for hyperparathyroidism (HPT) carries an increased risk for morbidity and failure to cure. Accurate preoperative localization minimizes operative risk but is often difficult to achieve in the reoperative setting. Four-dimensional computed tomography (4D-CT) is an emerging technique that uses functional parathyroid anatomy for precise preoperative localization. We evaluated 4D-CT as a tool for localization of hyperfunctioning parathyroid tissue in the reoperative setting. STUDY DESIGN: A prospective endocrine database was queried to identify 45 patients who underwent reoperative parathyroidectomy after preoperative localization using 4D-CT. The patients were categorized into 1 of 3 groups: group 1 included those who had previous neck surgery for non-HPT conditions; group 2 included those who had undergone a previously unsuccessful neck exploration for HPT; and group 3 included patients with HPT who had a previous neck exploration with resection of at least 1 hypercellular parathyroid. RESULTS: The sensitivity of 4D-CT for localization was 88% compared with 54% for sestamibi imaging. Four-dimensional CT more often correctly localized (p=0.0003) and lateralized (p=0.005) hyperfunctional parathyroid tissue than sestamibi did. Four-dimensional CT successfully localized hyperfunctional parathyroid tissue in 18 (82%) of 22 group 1 patients, 10 (91%) of 11 group 2 patients, and 8 (67%) of 12 group 3 patients. Three patients were lost to followup. At a mean followup of 9.8 months, 39 (93%) of 42 patients were surgically cured and 3 patients (7%; 2 in group 3) had persistent HPT. CONCLUSIONS: Four-dimensional-CT is an ideal tool for preoperative localization of hyperfunctioning parathyroid tissue in the reoperative setting. Localization and successful reoperation are most difficult in patients who have undergone an earlier operation that included resection of at least one hypercellular parathyroid suggesting multigland disease.     

Mouse Modifier Genes in Mammary Tumorigenesis and Metastasis

Tumorigenesis and metastasis are complex multistep processes. In addition to the numerous somatic mutations that facilitate cancer progression, there is abundant evidence that an individual’s genetic background not only contributes to overall cancer risk, but also specifically influences metastatic potential. The handful of human susceptibility genes that have been identified thus far do not fully account for hereditary cancer risk, and the discovery of additional susceptibility loci using population based studies is complex, time-consuming and expensive. Therefore, we and others have used a variety of mouse models to identify novel candidate susceptibility genes. Here we review how these mouse models have contributed to our understanding of the role of genetic background in modifying tumorigenesis and metastasis susceptibility.     

The genetics of intervertebral disc degeneration. Familial predisposition and heritability estimation

ObjectivesTo review current knowledge on heritability of intervertebral disc degeneration (IDD). IDD can contribute to the development of low back pain and acute lumbar radiculopathy. Dramatic change in the current view of risk factors for IDD from one where age and mechanical factors were paramount to the current theory that genetic risk factors are predominant, we thought that it is important to review the studies of the genetic influences on IDD beginning from familial aggregation and heritability estimation and finishing with specific studies of genes associated with IDD.MethodsA literature-based narrative review of English language medical literature.Results and conclusionsPrior research has demonstrated the existence of familial predisposition to IDD with generally high heritabilities that range from 34% to 61% in different spine locations. Segregation analysis shows that the mode of inheritance is complex with multiple factors and multiple genes likely involved in intergenerational transmission.     

The genetics of intervertebral disc degeneration. Associated genes

ObjectivesTo review current knowledge on genes associated with intervertebral disk degeneration.MethodsA literature-based narrative review of the English language medical literature.Results and conclusionsThere are a number of genes that have been associated with intervertebral disk degeneration in humans, including genes coding for collagen I, collagen IX (COL9A2 and COL9A3), collagen XI (COL11A2), IL-1, aggrecan, vitamin D receptor, MMP-3, and CILP. For specific genes and some environmental factors, gene–gene, gene–environment and gene–age interactions may exist. Candidate–gene association studies have limitations in detecting the genetic basis of the disease because this approach relies on having predicted the correct genes on the basis of a biological hypothesis or the location of known linkage regions. Additional studies, including linkage analyses and whole genome scan studies in different populations and whole range of ages, are required to improve our understanding of the influence of the aforementioned genes on intervertebral disk degeneration and identify novel genes.     

Gender Differences and Biomechanics in the 3000M Steeplechase Water Jump

Since 1996, women have been competing in the 3000m steeplechase race internationally. Whenever women and men both compete in similar events with different equipment (the barriers are lower for women) consideration should be given as to how techniques should be coached differently. This study investigated the differences in water-jump technique between men and women after accounting for differences in running speed and which techniques led to maintenance of race pace through the water-jump. Eighteen men and 18 women were filmed at two major track and field meets during the 2004 season. Peak Motus 8.2 was used to digitize all seven jumps from each athlete. Various characteristics of water-jump technique were measured or calculated and compared using two multiple linear regressions (one for men and one for women) to determine which characteristics led to maintaining race pace speeds through the water jump obstacle. Repeated measures ANOVA was used to determine any differences between men and women in the measured characteristics of technique.Velocity through the jump divided by race pace was predicted very well by approach velocity and landing distance for men and women. Other characteristics of the movement were non-significant. Differences between genders were found in: approach velocity, take-off distance, landing distance, push-off angle, velocity through jump, and exit velocity. Men and women steeplechasers must focus on approach velocity and landing distance to complete the water-jump close to their race pace. Coaches need to consider many characteristics of technique that differ between men and women.

Key points

• Women may need to be coached differently than men in the steeplechase water jump due to different techniques required.
• Men and women must focus on a high approach velocity to complete the steeplechase water jump successfully.
• Men and women must generate a relatively long landing distance to maintain velocity and keep from having to use extra energy exiting the water pit.
• Women''s race paces were affected more than men''s by the water jump in a negative way.

Key words: Track and field, athletics, hurdling, running, biomechanics.     

A randomized crossover trial of a wedged insole for treatment of knee osteoarthritis

OBJECTIVE: In uncontrolled studies, a lateral-wedge insole has reduced knee pain in patients with medial knee osteoarthritis (OA). The aim of this study was to test the efficacy of this simple, low-cost intervention for pain in patients with medial knee OA. METHODS: We conducted a double-blind, randomized, crossover trial designed to detect a small effect of treatment. Participants were at least 50 years of age and had medial joint space narrowing on posteroanterior semiflexed radiographs and scores indicating moderate pain for 2 of the 5 items on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale. Participants were randomized to receive a 5 degrees lateral-wedge insole or a neutral insole for 6 weeks. Following a 4-week washout period, participants crossed over to the other treatment for 6 weeks. Knee pain, the primary outcome, was assessed by the WOMAC pain scale (visual analog scale version). Secondary outcomes included the WOMAC disability subscale, overall knee pain, 50-feet walk time, chair-stand time, and use of medications for knee pain. RESULTS: Ninety patients were randomized. The mean difference in pain between the 2 treatments was 13.8 points on the WOMAC pain scale (95% confidence interval -3.9, 31.4 [P=0.13]). We observed similar small effects for the secondary outcomes. CONCLUSION: The effect of treatment with a lateral-wedge insole for knee OA was neither statistically significant nor clinically important.