Homozygous Type IX collagen variants (COL9A1, COL9A2, and COL9A3) causing recessive Stickler syndrome-Expanding the phenotype.

Stickler syndrome (SS) is characterized by ophthalmic, articular, orofacial, and auditory manifestations. SS is usually autosomal dominantly inherited with variants in COL2A1 or COL11A1. Recessive forms are rare but have been described with homozygous variants in COL9A1, COL9A2, and COL9A3 and compound heterozygous COL11A1 variants. This article expands phenotypic descriptions in recessive SS due to variants in genes encoding Type IX collagen. Clinical features were assessed in four families. Genomic DNA samples derived from venous blood were collected from family members. Six affected patients were identified from four pedigrees with variants in COL9A1 (one family, one patient), COL9A2 (two families, three patients), and COL9A3 (one family, two patients). Three variants were novel. All patients were highly myopic with congenital megalophthalmos and abnormal, hypoplastic vitreous gel, and all had sensorineural hearing loss. One patient had severe arthropathy. Congenital megalophthalmos and myopia are common to dominant and recessive forms of SS. Sensorineural hearing loss is more common and severe in recessive SS. We suggest that COL9A1, COL9A2, and COL9A3 be added to genetic screening panels for patients with congenital hearing loss. Although recessive SS is rare, early diagnosis would have a high impact for children with potentially dual sensory impairment, as well as identifying risk to future children.

A Comprehensive Single Institutional Review of 2 Years in a Designated Fast-Track Sarcoma Diagnostic Clinic Linked with a Sarcoma Specialist Advisory Group: Meeting the Target but Failing the Task?

Background. National guidelines prompted the implementation of a designated two-week wait referral pathway to facilitate the early diagnosis of sarcomas, to improve treatment outcomes. Methods. Patients referred to the Cambridge Sarcoma Diagnostic Clinic between January 2013 and December 2014 were identified through the electronic appointments system. Information was retrospectively retrieved about patient characteristics and details of the diagnostic pathway. Results. 17.3% of patients referred (69/397) were diagnosed with a malignancy. Of these, 59.3% (41/69) had primary sarcomas, 17.4% (12/69) had metastatic cancer, and 23.2% (16/69) had a different primary malignancy. 15% of the 41 sarcomas were <5 cm, 34% in the 5-10 cm range, and 51% >10 cm. Sarcomas diagnosed through this clinic represented 13% (41/315) of sarcomas managed at the centre during the same 2 years. Conclusion. While we achieved the target of 10% (41/397) sarcoma diagnosis rate in the rapid access clinic, only 15% of these were <5 cm better prognosis lesions. This calls into question the "real world" impact of such diagnostic clinics on early diagnosis of sarcomas. In order to enhance generic cancer diagnostic skills, training in these diagnostic clinics could be usefully integrated into national training curricula for both surgical and nonsurgical oncologists.

Foreign body granulomatous reaction associated with polyethelene 'Fiberwire(®)' suture material used in Achilles tendon repair.

Repair of acute Achilles tendon rupture is a common procedure. There are many accepted surgical techniques; suture selection is largely due to surgeon preference. We present a case report of a granulomatous reaction to suture material following Achilles tendon repair. 'Fiberwire(®)' is an increasingly popular suture material for the repair of tendons and ligamentous structures; the polyethelene braided structure with silicone and polyester coating provides high tensile strengths and good handling characteristics. Eight months following uneventful Achilles tendon repair surgery in an otherwise fit and well patient, pain, swelling and loss of function was noted. She required revision surgery with debridement and reconstruction of the tendo Achillis with flexor hallucis longus tendon transfer. Histology revealed a granulomatous reaction with giant cell response surrounding sections of the suture. Both the silicone coating of Fiberwire(®) and polyethylene core have the potential to cause a severe granulomatous reaction. We would advise caution in the use of this suture for tendo Achillis repair, and use the readily available alternatives.

Validation of clinical examination versus magnetic resonance imaging and arthroscopy for the detection of rotator cuff lesions.

Limited evidence exists regarding the validity of clinical examination for the detection of shoulder pathology. We therefore wished to establish the sensitivity, specificity, positive predictive value and negative predictive value of clinical tests and magnetic resonance imaging (MRI) in the diagnosis of rotator cuff disorders against findings at arthroscopy. Using recognised tests for specific shoulder lesions, 117 patients with shoulder symptoms awaiting surgery were examined in a standard manner. The diagnoses were categorised and compared with abnormalities found on MRI and at surgery. Results were cross-tabulated to determine the above parameters. Ninety-four patients formed the study group with a mean age of 51 years. The median duration of symptoms was 45 weeks. For clinical examination, sensitivity and specificity to detect a tear or rupture of supraspinatus were 30 % (16/54) and 38 % (15/40) and, for the detection of any pathology, were 94 % (67/71) and 22 % (5/23), respectively, compared with arthroscopy. Correspondingly, the sensitivity of MRI compared with arthroscopy to detect a tear or rupture of supraspinatus was 90 % (28/31) with a specificity of 70 % (46/53), whereas for the detection of any abnormality, the sensitivity was 92 % (65/71) with a specificity of 48 % (11/23). The sensitivity of detecting any rotator cuff abnormality is high when examination and MRI is compared with arthroscopy with the specificity being greater with MRI than examination. In patients with shoulder symptoms severe enough to consider surgery, clinical assessment followed by specific imaging may help define the pathology in order to direct appropriate management.

Multicentre trial of weekly risedronate on bone density in adults with cystic fibrosis.

BACKGROUND: The aim of this study was to assess the efficacy, tolerability and safety of risedronate in adults with CF. METHODS: Patients with a lumbar spine (LS), total hip (TH) or femoral neck (FN) bone mineral density (BMD) Z-score of -1 or less were randomised to receive risedronate 35 mg weekly or placebo, and calcium (1g)+vitamin D(3) (800IU). RESULTS: At baseline, BMD Z-scores in the risedronate (n=17) and placebo (n=19) groups were similar. By 24 months, 7/17 risedronate patients vs 0/19 placebo patients stopped the study medication due to bone pain. After 24 months treatment, the mean difference (95% CI) in change in LS, TH and FN BMD between the risedronate vs placebo groups was 4.3% (0.4, 8.2) p=0.03; 4.0% (-0.5, 8.6) p=0.08; and 2.4% (-3.5, 8.2) p=0.41. CONCLUSIONS: After two years treatment there was a significant increase in LS BMD with weekly risedronate compared to placebo.

MR-guided direct arthrography of the hip.

PURPOSE: To develop an MR-guided technique for direct magnetic resonance arthrography (DMRA) of the hip using a conventional 1.5 Tesla (T) MRI scanner. MATERIALS AND METHODS: Interactive versions of standard single-shot fast spin echo, coherent gradient echo, and fully balanced steady-state free precession sequences were developed, together with the ability to operate the scanner from within the magnet room. Initial optimization was performed using ex vivo animal joints. After informed consent, five patients underwent DMRA using dilute gadolinium as the contrast medium. RESULTS: The procedure was successful in all five patients and diagnostic quality MR arthrography studies were obtained in all cases. The time taken from the initial placement of skin marker to the introduction of contrast medium reduced with successive patients: 26, 22, and 19 min with the final two studies taking 13 min each. CONCLUSION: This work demonstrates the feasibility of performing DMRA using MR guidance, avoiding the need for X-ray fluoroscopy facilities but exploiting the available imaging performance of a high-field closed-bore MR system. The use of an in room control and display system together with interactive fluoroscopic imaging sequences simplifies the positioning of the needle and allows rapid confirmation of an intra-articular injection.

Imaging modalities in the evaluation of soft tissue complaints.

A number of imaging modalities are available for the assessment of soft tissue complaints. The strengths and advantages of each modality must be seen in the context of any corresponding weakness or disadvantage. The sensitivity and specificity of the imaging technique must also be understood. In this article, each main radiological technique will be considered in turn. Fundamental technical aspects and common variations of the basic imaging theme will be explained and their relative strengths and limitations will be explored. Typical common clinical uses in the context of soft-tissue complaints will be considered.

Soft-tissue masses in the shoulder girdle: an imaging perspective.

We discuss the radiological assessment of soft-tissue masses presenting in the shoulder girdle and emphasise the relative strengths and weaknesses of the different imaging modalities available. The appearances of the common benign and malignant soft-tissue tumours are presented together with conditions that present with specific imaging features around the shoulder region.

MRI of the ankle: effect on diagnostic confidence and patient management.

OBJECTIVE: The purpose of our study was to quantify the impact that MRI of the ankle has on a surgeon's diagnosis and diagnostic confidence and on patient management. SUBJECTS AND METHODS: A prospective controlled observational study was performed with 91 consecutive referrals (53 males, 38 females; age range, 13-76 years; mean age, 40.6 years) from a single orthopedic foot and ankle surgeon to a regional teaching hospital for ankle MRI. Measurements of diagnostic confidence using a visual analogue scale (VAS) were made both before and after the MRI examination in each case. Proposed management was also recorded before imaging and then with benefit of the MRI result. Finally, the surgeon provided a subjective statement regarding the perceived usefulness of the MRI examination when the patient was subsequently reviewed in the clinic. RESULTS: There was a significant overall change in diagnostic confidence in 65 (71%) cases. The number of diagnoses reduced from an average per patient of 2.3 (95% CI, 2.09-2.44) to 1.2 (95% CI, 1.05-1.39), and in 157 (69%) of all diagnoses entertained, there was a significant change in the confidence with which they were considered after imaging. Management plans changed in 32 (35%) of the patients, and in 31% of those patients for whom plans were changed, a less invasive plan was adopted. Overall, the surgeon thought that understanding of the patient's disease had either depended on MRI or had been substantially improved by it in 60 (66%) cases. CONCLUSION: MRI of the ankle influences clinicians' diagnoses and management plans.

Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy.

BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti-tumor necrosis factor-alpha (TNF-alpha) therapy. METHODS AND RESULTS: Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-alpha therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively; P = 0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein (R2 = 0.701; P < 0.0001). Aortic PWV was reduced significantly by anti-TNF-alpha therapy (8.82+/-2.04 versus 7.94+/-1.86 versus 7.68+/-1.56 m/s at weeks 0, 4, and 12, respectively; P < 0.001); concomitantly, endothelial function improved. CONCLUSIONS: RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-alpha therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.

Can 16-detector multislice CT exclude skeletal lesions during tumour staging? Implications for the cancer patient.

Current imaging guidelines recommend that many cancer patients undergo soft-tissue staging by computed tomography (CT) whilst the bones are imaged by skeletal scintigraphy (bone scan). New CT technology has now made it feasible, for the first time, to perform a detailed whole-body skeletal CT. This advancement could save patients from having to undergo duplicate investigations. Forty-three patients with known malignancy were investigated for bone metastasis using skeletal scintigraphy and 16-detector multislice CT. Both studies were performed within six weeks of each other. Whole-body images were taken 4 h after injection of 500 Mbq (99m)Tc-MDP using a gamma camera. CT was performed on a 16-detector multislice CT machine from the vertex to the knee. The examinations were reported independently and discordant results were compared at follow-up. Statistical equivalence between the two techniques was tested using the Newcombe-Wilson method within the pre-specified equivalence limits of +/-20%. Scintigraphy detected bone metastases in 14/43 and CT in 13/43 patients. There were seven discordances; four cases were positive on scintigraphy, but negative on CT; three cases were positive on CT and negative on scintigraphy. There was equivalence between scintigraphy and CT in detecting bone metastases within +/-19% equivalence limits. Patients who have undergone full whole-body staging on 16-detector CT may not need additional skeletal scintigraphy. This should shorten the cancer patient's diagnostic pathway.

Giant atypical ossifying fibromyxoid tumour of the calf.

We present a case of giant atypical ossifying fibromyxoid tumour (OFMT) of soft tissue, occurring in the calf, in a 77-year-old woman. The patient presented with a history of bleeding ulcer over a calf lump that had been present for over 4 years. Clinical presentation, radiological features and histopathologic findings are described, and the relevant literature is reviewed.

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study.

Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P = 0.011) and a non-significant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P = 0.005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone-specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.

Lack of effect of intravenous pamidronate on fracture incidence and bone mineral density after orthotopic liver transplantation.

BACKGROUND/AIMS: Increased rates of bone loss and fracture have been reported after liver transplantation. The aim of this study was to investigate the effects of a pre-transplant infusion of pamidronate on fracture incidence and bone loss during the first year after transplantation. METHODS: Ninety-nine adults awaiting orthotopic liver transplantation (OLT) were randomised to pamidronate or no treatment. Spinal X-rays were obtained at baseline and after 12 months. Bone mineral density (BMD) was measured at the lumbar spine (L1-4) and femoral neck at baseline, and 3, 6, and 12 months after OLT. RESULTS: The incidence of fractures in the first year after OLT was 8%, four patients within the pamidronate treated group and two in the untreated group developing fractures (P=0.40). No significant spinal bone loss occurred in either group during the first year. However, significant and sustained bone loss occurred at the femoral neck in both groups. No significant differences were seen between pamidronate treated or untreated groups at either site. CONCLUSIONS: Pamidronate in the regimen used had no significant effect on fracture rate or BMD post-transplant. The low incidence of fracture and absence of spinal bone loss indicate that bone disease after liver transplantation may be less common than previously reported.

Ultrasound of the male anterior urethra.

Ascending and descending techniques are used to demonstrate the male anterior urethra. The authors developed an ultrasound approach with the patient compressing his own urethra manually during voiding to achieve distension of the urethra with urine. The subsequent sonourethrography is more accurate than conventional fluoroscopic contrast studies in defining urethral filling defects and is as accurate for the demonstration of strictures. The technique has replaced contrast urethrography at the authors' institutions for the routine evaluation of the anterior urethra.