Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS. METHODS: Seventy-one adult males (median age 41 years, range 18-64) with 47, XXY KS were consecutively enrolled by two Endocrinology and Andrology Units (IRCCS Humanitas Research Hospital in Milan and ASST Spedali Civili in Brescia). Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density (BMD) at lumbar spine, femoral neck and total hip, TBS and body composition. Prevalence of VFs was assessed by quantitative morphometry on lateral spine X-rays. RESULTS: VFs were detected in 14 patients (19.7%), without significant association with low BMD (p = 0.912). In univariate logistic regression analysis, VFs were significantly associated with truncal/leg fat ratio (OR 2.32 per tertile; 95% CI 1.05-5.15; p = 0.038), whereas impaired TBS (detected in 23.4% of subjects) was associated with older age at study entry (p = 0.001) and at diagnosis of disease (p = 0.015), body mass index (BMI; p = 0.001), waist circumference (p = 0.007), fat mass index (FMI; p < 0.001), FMI/lean mass index (LMI) ratio (p = 0.001). Prevalence of VFs was not significantly different between subjects with impaired TBS as compared to those with normal TBS (26.7 vs. 18.4%; p = 0.485). Skeletal end-points were not significantly associated with duration of testosterone replacement therapy and serum testosterone and 25hydroxyvitamin D values. CONCLUSION: Body composition might influence bone quality and risk of VFs in subjects with KS.

Mirrors used in the LIGO interferometers for first detection of gravitational waves.

For the first time, direct detection of gravitational waves occurred in the Laser Interferometer Gravitational-wave Observatory (LIGO) interferometers. These advanced detectors require large fused silica mirrors with optical and mechanical properties and have never been reached until now. This paper details the main achievements of these ion beam sputtering coatings.

Phase I and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours.

BACKGROUND: NGR-hTNF exploits the peptide asparagine-glycine-arginine (NGR) for selectively targeting tumour necrosis factor (TNF) to CD13-overexpressing tumour vessels. Maximum-tolerated dose (MTD) of NGR-hTNF was previously established at 45 µg m(-2) as 1-h infusion, with dose-limiting toxicity being grade 3 infusion-related reactions. We explored further dose escalation by slowing infusion rate (2-h) and using premedication (paracetamol). METHODS: Four patients entered each of 12 dose levels (n=48; 60-325 µg m(-2)). Pharmacokinetics, soluble TNF receptors (sTNF-R1/sTNF-R2), and volume transfer constant (K(trans)) by dynamic imaging (dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)) were assessed pre- and post-treatment. RESULTS: Common related toxicity included grade 1/2 chills (58%). Maximum-tolerated dose was not reached. Both C(max) (P<0.0001) and area under the plasma concentration-time curve (P=0.0001) increased proportionally with dose. Post-treatment levels of sTNF-R2 peaked significantly higher than sTNF-R1 (P<0.0001). Changes in sTNF-Rs, however, did not differ across dose levels, suggesting a plateau effect in shedding kinetics. As best response, 12/41 evaluable patients (29%) had stable disease. By DCE-MRI, 28/37 assessed patients (76%) had reduced post-treatment K(trans) values (P<0.0001), which inversely correlated with NGR-hTNF C(max) (P=0.03) and baseline K(trans) values (P<0.0001). Lower sTNF-R2 levels and greater K(trans) decreases after first cycle were associated with improved survival. CONCLUSION: asparagine-glycine-arginine-hTNF can be safely escalated at doses higher than MTD and induces low receptors shedding and early antivascular effects.

A new type of Hypersensitivity Pneumonitis: salami brusher's disease.

We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.

Magnetic resonance imaging in the initial staging of Hodgkin's disease and non-Hodgkin lymphoma.

Seventy-four consecutive previously untreated patients with Hodgkin's disease (HD) and non-Hodgkin lymphomas (NHL) were evaluated with chest, abdominal and pelvic magnetic resonance (MRI) for initial staging. All patients underwent routine radiological staging procedures which included chest radiographs and lymphography (LAG). These studies were followed in most of cases by laparoscopy, during which biopsies of the liver and the spleen were taken, and bone marrow aspiration and histology. A correlation of the results of MRI with both other imaging studies and histopathologic diagnoses was performed, and discordant cases were assessed to determine the impact on clinical staging. Additional evidence of disease involvement was provided mainly in the chest, where MRI demonstrated the presence of unsuspected disease in 21% of involved patients (9 of 42). Retroperitoneal lymph nodes were correctly assessed in 97% of cases if MRI was compared with LAG. Extranodal abdominal disease was identified both in the spleen (14%) and in the liver (1%). Bone marrow abnormalities were detected in 19% of patients (14 of 74). MRI findings influenced the staging of HD and NHL patients in 11 of 74 cases (15%).

MRI as an adjunct to echocardiography for the diagnostic imaging of cardiac masses.

Nine patients underwent magnetic resonance imaging (MRI) as part of the diagnostic evaluation for cardiac masses; eight of them had been preliminarily studied by 2D-echocardiography (US). MRI did not add to the US diagnostic information in patients affected by intracavitary masses. It represented the definitive diagnostic modality in two patients with intramural pathology: one with ventricular rhabdomyoma, the second with an echinococcyal cyst located within the left atrial wall. The complementary role of MRI to US in cardiac masses is discussed.

Magnetic resonance imaging of the gastrointestinal tract: investigation of baby milk as a low cost contrast medium.

After the incidental observation of the high signal intensity of the upper GI tract in a nourished baby, we tested eight baby milks; five different fresh commercial milks, one sweetened and condensed and two lyophilized milks in order to compare their ability to contrast MR images. The images were obtained with a 1.5 T magnet whereas the "in vitro" water proton relaxation time (T1 and T2) measurements were carried out at 0.5 T. After having selected the most effective lyophilized product, that was prepared according to the manufacturer's instructions, a group of 23 adult patients, 17 males and 6 females, with a mean age of 55.8 years (range 37 to 71 years) were examined. Thirteen patients had gastric cancer and ten patients had rectal or rectosigmoid junction tumors. The most effective imaging sequence was a spin-echo T1.w. After oral intake of milk a good contrast of the stomach, with sufficient distribution in the duodenum and the very proximal bowel, was achieved in all 13 patients with gastric cancer, as was a good depiction of the rectum and the recto-sigmoid junction after enema achieved in the 10 patients with rectal cancers. Disadvantages of lyophilized milk as a contrast agent are due to partial intestinal absorption, inhomogeneous distribution and irregular intestinal passage, whereas a clear advantage of lyophilized milk as a contrast agent is its good acceptance and palatable, inexpensive and non invasive properties. Because of these limitations lyophilized milk cannot be considered a real oral contrast medium but it can enhance MR imaging of the upper abdomen, and mainly of the lower GI tract in infants and adults.

Accuracy of the double contrast enema in evaluation of the abdominal diffusion of ovarian carcinoma.

The results of 103 double contrast enemas in 72 patients with ovarian carcinoma (stage III and IV) were compared with laparoscopic and/or laparotomic findings at comparable times. The evaluation of the validity of radiology in detecting the presence of abdominal disease showed an 84% overall accuracy, 75% specificity and 86% sensitivity. The accuracy in detecting signs of adhesion and parietal infiltration of the large bowel was 76.3%, due to the limited size of most of the lesions. Forty-seven of the 72 patients underwent a double contrast enema and laparoscopy during presurgical staging: accuracy in detecting lesions was the same for both examinations (80.4%). When double contrast enema and laparoscopy were used together in the evaluation of abdominal extension of the disease, the diagnostic accuracy rose to 93.6%.

Bone lesion in a patient with transplanted liver for a metastatic carcinoid. The role of somatostatin receptor scintigraphy.

A patient who had previously undergone ileal resection and liver transplantation for a gastroenteropancreatic (GEP) tumor was evaluated with somatostatin receptor scintigraphy (SRS) using 111In-DTPA-D-Phe1-pentetreotide. Eighteen months after surgery, during follow-up procedures, conventional imaging techniques (ultrasound, computed tomography, magnetic resonance imaging) only showed a relapse in the gastropancreatic lymph nodes, while SRS demonstrated skeletal spread. This case report emphasizes the clinical impact of SRS on the management of patients affected by neuroendocrine gastroenteropancreatic tumors.

The role of magnetic resonance imaging in the evaluation of neoplastic lesions of the breast.

Thirty-seven patients were evaluated for suspected breast cancer by magnetic resonance imaging (MRI) using 0.5- and 1.5-Tesla. We examined the patterns in breast images and the use of MRI in evaluating neoplasms. At the moment the cost/benefit ratio is unfavorable, mainly because of the availability of alternative methods of high accuracy and low cost, like mammography and ultrasonography. Furthermore fine needle aspiration biopsy is not possible with MRI. The widespread use of MRI for breast pathology seems not to be justified by the results obtained.

Reliability of diagnostic imaging after orchiectomy alone in follow-up of clinical stage I testicular carcinoma: excessive cost with potential risk.

From 1981 to 1984, 86 consecutive patients with previously untreated nonseminomatous testicular carcinoma were classified as clinical radiological stage I and treated with orchiectomy alone. The follow-up program included chest x-ray and lymphangiography (LAG) every month and abdominal computed tomography (CT) bimonthly. All patients were followed for 15 to 63 months after orchiectomy (median 32 mo.). Metastases developed in 23 patients (26.7%) and in 13/23 there was retroperitoneal lymphadenopathy. Time of relapse after orchiectomy ranged from 2 to 36 months (median 7 mo.) with a shorter interval for chest (4 mo.) compared with retroperitoneal metastases (7 mo.). Lung metastases were readily identified at an early stage (less than 2 cm) whereas more than one-third of retroperitoneal nodal metastases were greater than 5 cm at time of diagnosis. LAG detected metastases in 8/11 patients (72.7%), abdominal CT in 8/10 (80%), and both together (LAG and CT) 7/8 (87.5%). In clinical stage I nonseminomatous testicular carcinoma, the high incidence of concomitant but often asymptomatic regional and distant metastases and the relatively high cost and inconvenience of follow-up using abdominal CT imaging, LAG and chest x-ray suggest that orchiectomy is best combined with retroperitoneal node dissection at time of initial presentation to insure more accurate and safe staging of tumor dissemination.

Transfusional Mansonella perstans microfilariasis.

Mansonella perstans filariasis is widely distributed across the center of Africa and equatorial America. We describe a case of post-transfusional M. perstans microfilariasis in a young child, affected with severe Plasmodium falciparum malaria, admitted in Goundi Hospital in South of Chad. A decrease of M. perstans microfilariasis in the patient's blood was observed, with no subsequent development of either clinical symptoms or eosinophilia. We suggest that, in endemic areas, transfused M. perstans microfilariae may be cleared from the blood over relatively short periods of time. It is likely that only adult worms are responsible for symptoms and eosinophilia, whereas microfilariae in the bloodstream are unable to give clinical manifestations.

The osteosarcoma amputation stump: a clinico-radiographical correlation.

The radiological picture of the amputation stump after osteosarcoma was reviewed in 75 cases, in which postoperative follow-up ranged from a minimum four months, to a maximum of over 12 years. In 67/75 cases (89%) no recurrence was observed; in 8/75 cases (11%) a local neoplastic recurrency was confirmed on clinical and histopathological grounds. The usual aspects of late modifications induced by surgery include osteoporosis of the residual bone, which may assume a geographical pattern, with thinning of the stump apex and formation of a periosteal spur directed towards the soft tissues. The typical pattern of locally recurrent osteosarcoma is that of an infiltrating soft tissue mass with bone erosion and irregular flake-like calcifications. All these signs are presented and discussed in order to give a practical guideline to the differential diagnosis between surgery-induced modifications and local neoplastic recurrences.

Thyroid gland and pulmonary hypertension. What's the link?

Both hyperthyroidism and hypothyroidism produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic or pulmonary vascular resistance. In almost all cases these cardiovascular changes are reversible when the underlying thyroid disorder is recognized and treated. Pulmonary hypertension (PAH) has been associated with thyroid dysfunction, but primarily with hyperthyroidism. The vast majority of patients with this form of PAH are usually older with toxic multinodular goitre. Data currently available suggest a direct influence of TH on pulmonary vasculature. Possible mechanisms include: 1) enhanced catecholamine sensitivity, causing pulmonary vasoconstriction, a reduction in pulmonary vascular compliance and an increase in vascular resistance; 2) increased metabolism of intrinsic pulmonary vasodilating substances (prostacyclin, nitric oxide); 3) decreased or impaired metabolism of vascontrictors (serotonin, endothelin 1 and tromboxane). In some cases (Graves's and Hashimoto's disease) and an autoimmune process inducing endothelial damage may play a key role. Future studies should focus on discovering the immunogenetic overlap between autoimmune thyroid diseases and PAH: common human leukocyte antigen alleles, susceptibility loci and so on. Such an understanding of the genetic and immune factors may ultimately lead to novel effective approaches in the treatment of PAH. At present, thyroid function tests should be considered in the investigation of all patients with PAH.

Prospective comparison of computed tomography enterography and magnetic resonance enterography for assessment of disease activity and complications in ileocolonic Crohn's disease.

BACKGROUND: Studies comparing magnetic resonance enterography (MRE) and computerized tomography enterography (CTE) for Crohn's disease (CD) are scarce. METHODS: The aim of this study was to prospectively compare the sensitivity, specificity, and accuracy of abdominal MRE and CTE to assess disease activity and complications (fistulas, strictures) in ileocolonic CD. A total of 44 patients (23 male; 21 female; mean age 44) with ileocolonic CD underwent both MR and CT in a short time interval (mean 5 days). A 16-slice CT with intravenous contrast and an MRI with oral and paramagnetic intravenous contrast were performed. Ileocolonoscopy was used as the reference standard. Sensitivity values of CT and MR for detection of extraenteric signs of disease were compared with the McNemar test, with results of imaging studies, surgery, and physical examination as reference standards. RESULTS: No significant differences in sensitivity, specificity, and accuracy were observed between MRE and CTE regarding the following parameters at the patient level: localization of CD (P = 1.0), bowel wall thickening (P = 1.0), bowel wall enhancement (P = 1.0), enteroenteric fistulas (P = 0.08), detection of abdominal nodes (P = 1.0), and perivisceral fat enhancement (P = 0.31). MR was significantly superior compared to CT in detecting strictures (P = 0.04). Per segment analysis showed that MRE was significantly superior to CTE in detecting ileal wall enhancement (P = 0.02). CONCLUSIONS: MR and CT are equally accurate to assess disease activity and bowel damage in CD. MR may be superior to CT in detecting intestinal strictures and ileal wall enhancement. MR may represent an alternative technique to CT in assessing ileocolonic CD.

[Radiographic evaluation of the amputation stump in osteosarcoma]. / Valutazione radiografica del moncone di amputazione per osteosarcoma.

The radiological picture of the amputation stump for osteosarcoma was revised on 57 cases, in which a follow-up after surgery was possible for at least 4 months, with a maximum of over 12 years. In 51/57 cases (89%) no recurrency was observed; in 6/57 cases (11%) a local neoplastic recurrency was confirmed on clinical and histopathological grounds. The usual aspects of late modifications induced by surgery is osteoporosis of the residual bone, which may assume a geographical pattern, with thinning of the stump apex and formation of a periosteal spur directed towards to soft tissues. The typical pattern of the locally recurrent osteosarcoma is that of an infiltrating soft tissue mass with bone erosion and irregular flake-like calcifications. All these signs are evaluated and discussed in order to give a practical guideline to the differential diagnosis between surgery-induced modifications and local neoplastic recurrencies.

[Feasibility of magnetic resonance-guided fine-needle percutaneous biopsy]. / Possibilità di utilizzazione della risonanza magnetica nella guida alla biopsia percutanea con ago sottile.

Fluoroscopic, US, and CT guidance to aspiration cytology are valuable tools for oncologic diagnosis. MR imaging is now replacing CT as the imaging method of choice to guide biopsy mainly in the abdomen and pelvis. The standard needles used for CT-guided biopsy are unsuitable for MR guidance because ferromagnetic artifacts shade the underlying anatomy. A new needle specifically designed for MR guidance allowed MR-guided aspiration biopsies to be carried out in a group of 17 patients with different neoplastic diseases. To locate the lesion and to assess its depth, a glass pipette containing a diluted solution of paramagnetic contrast medium (Gd-DTPA) was placed on the skin surface. In 13/17 patients (76.5%), biopsy was successful and histology and/or cytology allowed a diagnosis to be made. In spite of their longer measurement times, T1-weighted SE images clearly demonstrated both needle and lesion. On the contrary, fast images (FLASH, 15 degrees-90 degrees), with/without breath holding, although much shorter (7 s), were often useless, due to artifacts, mainly in small lesions.

[Current role of conventional tomography in the staging of pulmonary neoplasms. Reflections based on the comparison of tomography-magnetic resonance in 81 cases]. / Ruolo attuale della tomografia tradizionale nella stadiazione delle neoplasie polmonari. Riflessioni sulla base del confronto tomografia-risonanza magnetica in 81 casi.

The preoperative conventional tomographic and Magnetic Resonance images were reviewed of 81 patients affected with bronchogenic carcinoma; all patients underwent surgery 1986 to 1988. Radiological findings were compared with surgical and pathological results to evaluate the actual role of conventional tomography in the staging of bronchogenic carcinoma. MR Imaging proved to be more useful in the evaluation of mediastinal and hilar lymph nodes. As for mediastinal node status, conventional tomography had 23.5% sensitivity, 90.6% specificity, and 76.5% overall accuracy; MR Imaging had 82.3% sensitivity, 84.4% specificity, and 84% overall accuracy. As for hilar adenopathies, tomographic sensitivity, specificity and overall accuracy were 53.3%, 72.5%, and 65.4% versus 50%, 82.3% and 70.4% with MR Imaging. Tomography was slightly superior in identifying the primary tumor (97.5% versus 92.6% for MR), as well as in the demonstration of central bronchial involvement (100% for conventional tomography versus 50% for MR Imaging). Conventional tomography is useful as a complementary technique to MR Imaging in the preoperative staging of bronchogenic carcinoma when information on central bronchial involvement is needed.