Bone marrow microenvironment and the progression of multiple myeloma.

The BM microenvironment in MM, in terms of adhesive features, is well organized to entrap circulating precursors with BM-seeking properties and is able to produce cytokines that offer them the optimal conditions for local growth and final differentiation. Likewise, the malignant B cell clone is equipped with adhesion molecules which enable the cell to establish close contacts with BM stromal cells. Furthermore a number of cytokines are released including IL-1 beta and M-CSF activating BM stromal cells to produce other cytokines, such as IL-6, that stimulate the proliferation of plasma cells. Finally, most cytokines produced locally, including IL-1 beta, TNF-beta, M-CSF, IL-3 and IL-6, also have OAF properties, explaining why the expansion of the B cell clone parallels the activation and numerical increase of the osteoclast population.     

Carotid endarterectomy: Importance of cranial nerve anatomy

A retrospective study of 100 consecutive cases of carotid endarterectomy was performed. Special attention was given to the incidence, clinical significance, and prevention of cranial nerve injury. The operative mortality was 1%, and there were no perioperative strokes. There was clinical evidence of 22 cranial nerve injuries. Nineteen injuries were temporary, resulting in a 3% incidence of permanent cranial nerve deficit. The clinical anatomy of cranial nerves encountered during carotid endarterectomy is reviewed. Technical suggestions to minimize cranial nerve injury based on a thorough knowledge of this anatomy are provided. The relationship of laryngeal physiology and vagus nerve anatomy indicates that unilateral vocal cord dysfunction may be asymptomatic. Bilateral nerve injury can cause potentially fatal airway obstruction, which may be unrecognized until after the second operation. Preoperative laryngoscopy prior to carotid endarterectomy is suggested in patients with a history of prior cardiac or neck surgery and those scheduled for the second of staged bilateral carotid procedures.     

Rapid pain relief and remission of sternocostoclavicular hyperostosis after intravenous ibandronate therapy

Sternocostoclavicular hyperostosis (SCCH) is an infrequent but painful, localized disturbance of bone metabolism of unknown etiology. The diagnosis of SCCH is generally one of exclusion, and it is therefore frequently missed or delayed, leaving patients with pain that frequently fails to respond to standard analgesic therapy. Consequently, SCCH leads to significantly impaired quality of life. Characteristic increased localized bone turnover and inflammatory osteitis provide a strong rationale for using intravenous bisphosphonates to treat the condition. We report on three patients with long-standing, treatment-refractory SCCH in whom intravenous ibandronate injections (a single administration of 4 mg followed by 2 mg every 3 months for up to a year) produced prompt, dramatic, persistent pain relief and resolution of the other symptoms of the disease. We also review recent evidence suggesting that SCCH is more common than generally believed and that technetium-99 bone scanning can aid in making an accurate diagnosis.     

Transaxillary thoracoscopically assisted sympathectomy for nonhealing ulcers in scleroderma: a case report of successful treatment

We describe the successful treatment of a patient with chronic nonhealing ulcers caused by scleroderma refractory to medical therapy. This patient underwent a successful, transaxillary, thoracoscopically assisted, limited sympathectomy that resulted in healing of her ulcers and resolution of pain in the affected hand.     

Comparative effects of teriparatide and risedronate in glucocorticoid‐induced osteoporosis in men: 18‐month results of the EuroGIOPs trial

Data on treatment of glucocorticoid‐induced osteoporosis (GIO) in men are scarce. We performed a randomized, open‐label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T‐score ≤ –1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L₁–L₃) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high‐resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X‐ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18‐month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE‐derived strength than risedronate.     

Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study

The aim of this study was to assess the effect of treatment with risedronate 5 mg daily relative to control in men with primary or secondary osteoporosis over 2 years. Osteoporosis is a common condition in men that can have serious clinical consequences. In an earlier interim report, we found that 1 year of risedronate therapy resulted in significant increases in bone mineral density (BMD) and a significant reduction in vertebral fractures compared to control in men with osteoporosis. We conducted an open-label, prospective, match-control trial on men with primary or secondary osteoporosis in a single center, outpatient setting. Men with primary or secondary osteoporosis, as defined by a baseline lumbar spine BMD T-score ≤ −2.5 and a baseline femoral neck BMD T-score ≤ 2.0, were eligible for this study. Patients who had been treated with bisphosphonates or fluoride within the last 12 months were excluded. A total of 316 men were randomized to risedronate (n = 158) or control (n = 158). Patients were stratified by the presence of prevalent vertebral fractures at baseline and case by case allocated to either daily treatment with risedronate 5 mg daily plus calcium (1,000 mg) and vitamin D (800 IU) or to a control group (daily alfacalcidol (1 μg) plus calcium (500 mg) for those with prevalent vertebral fractures; daily vitamin D (800 IU) plus calcium (1,200 mg) for those without previous vertebral fractures). Primary study end points were identified prior to study initiation as the incidence of new vertebral fractures and changes in BMD at the lumbar spine, femoral neck, and total hip. Other end points included incidence of nonvertebral fractures and change in body height and back pain. Compared to control, the incidence of new vertebral fractures was significantly reduced in the risedronate 5 mg daily group at 2 years [14/152 (9.2%) for risedronate vs. 35/148 (23.6%) for control (61% risk reduction; P = 0.0026)]. Treatment with risedronate 5 mg daily also resulted in significant improvements in BMD at 2 years at all three skeletal sites (lumbar spine, 6.5 vs. 2.2%; femoral neck, 3.2 vs. 0.6%; total hip, 4.4 vs. 0.4% (P < 0.001 for all treatment comparisons). Significant reductions in the incidence of nonvertebral fractures (11.8 vs. 22.3%; P = 0.032), average loss in height, and back pain were also observed in risedronate-treated patients relative to control. In this 2-year study, daily 5 mg risedronate significantly reduced the risk of vertebral and nonvertebral fractures, improved BMD, decreased height loss, and reduced back pain in men with osteoporosis. Efficacy was sustained over 2 years; a consistent 60–61% risk reduction in vertebral fractures was observed at 1 and 2 years, respectively. These data demonstrate that daily risedronate is effective long-term therapy for men with primary or secondary osteoporosis.     

Follow-up of mediastinal lymphoma: role of ultrasonography

PURPOSE: Patients with lymphoma are often young and require long and intensive treatment, the toxic effects of which compound the impact of frequent radiological examinations. Computed tomography (CT) is of great value in the evaluation of the mediastinum, which is frequently involved by the disease, but carries a high radiation load. Ultrasonography (US) has therefore been proposed as an alternative procedure to evaluate response to treatment. Major advantages include good compliance, absence of patient risks, low cost, easy reproducibility, dynamic images enabling multiplanar evaluation and qualitative and quantitative criteria. The purpose of this study was to investigate the role of US in evaluating response to treatment in patients with mediastinal lymphomas using CT as the gold standard. MATERIALS AND METHODS: In 2005, 12 patients were evaluated by chest X-ray, mediastinal sonography and contrast-enhanced CT (gold standard). Each mediastinal region was accurately assessed for adenopathies. Lymph nodes were studied by evaluating their structure and morphology, measuring their size and classifying them according to location. RESULTS: US proved to be more sensitive and accurate (93%) than X-ray [66% sensitivity and 68% diagnostic accuracy (DA)]. In particular, the best sensitivity values were observed in the supraaortic (97% vs. 55%), prevascular (97% vs. 39%) and paratracheal (87% vs. 77%) regions and in the aortopulmonary window (80% vs. 0%). Deeper mediastinal compartments (subcarinal region and posterior mediastinum) could not be assessed. X-ray proved to be superior in hilar adenopathies only. US provides qualitative information (hypoechoic or hyperechoic tissues) in addition to quantitative data (maximum diameter of each lymph node) it shares with CT. DISCUSSION.: Compared with X-ray, US allows for a better evaluation of the anterior mediastinal regions, showing small, central adenopathies that do not alter the mediastinal lines on X-ray. It is, however, of very limited value in the evaluation of posterior compartments because of their deep location. US adds qualitative criteria to the quantitative criteria typical of CT. Limitations of mediastinal US include site of adenopathies, dependence on the patient's characteristics (body habit, concurrent diseases and chest anatomy) and dependence on the operator. CONCLUSIONS: US may have a specific role in monitoring patients with mediastinal adenopathies, providing early indications on possible response to treatment and allowing the frequency of CT follow-up scans to be reduced. In conclusion, US may be used to complement, but not replace CT, which remains the gold standard.