Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors.

OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.

Polytherapy in bone regeneration: clinical applications and preliminary considerations.

Polytherapy, namely the simultaneous application of three fundamental elements necessary for bone regeneration (growth factors, osteogenic cells and osteoconductive scaffolds) seems to lead to a very high success rate in the treatment of complex non-union (NU) cases and critical bone defects. NU are reported in 5-10% of long bone fractures. The use of autologous bone grafts has been long-considered the gold standard for the treatment of these cases. However the harvesting procedure from the iliac crest increases surgery time and presents some donor site complications which may be elevated. In recent years, surgeons have some alternatives to autologous grafting such as: application of organic or synthetic bone substitute, application of mesenchymal stromal cells (MSC) or growth factors (GF). In the literature there are many studies available about their application in monotherapy, but unfortunately the healing rate doesn't exceed 90%. Polytherapy seems to be a logical option to improve the healing rate, nevertheless, there are not still extensive studies that validate this strategy and moreover, some questions are not resolved.

Treatment of long bone non-unions with polytherapy: indications and clinical results.

The incidence of long bone non-unions has been estimated to range between 5 and 10%. Autologous bone graft usually harvested from the iliac crest continues to be the gold standard for biological enhancement of atrophic non-unions. However, its use has been hampered by minor and major donor site complications. Moreover despite possessing the properties of osteogenecity, osteoconductivity and some osteoinductivity the overall results of treatment have not been consistent with disappointing success rates at times. The concept of polytherapy for the treatment of non-unions, namely the simultaneous application of the three fundamental elements of the diamond concept, osteoprogenitor cells, growth factor and osteoconductive scaffold, appears to be an attractive alternative but more studies are desirable to validate this strategy.

Tibial pilon fractures: which method of treatment?

A comprehensive review of the existing literature, related to treatment options and management principles of pilon fractures was performed, and its results are presented. The identified series advocate in favour of a number of different treatment strategies and fixation methods. Decision making was mostly dependent on the severity of the local injury, the fracture pattern, the condition of the soft tissues, patient's profile and surgical expertise. External fixation and conservative treatment did not provide sufficient articular congruence in many cases. Internal fixation allowed excellent restoration of joint congruity in Rüedi type I and II fractures. A staged approach, consisting of fibular plating and temporary bridging external fixation, later substituted by an internal minimal invasive osteosynthesis or by a definitive external fixation, was favourable for Rüedi type III fractures. Closed pilon fractures with bad soft tissue conditions (Tscherne ≥ 3) or open pilon fractures are regarded as contraindication of open reduction plate fixation. Anatomic reduction of the fracture, restoration of joint's congruence, reconstruction of the posterior column, with minimal soft tissue insult, were all highlighted as of paramount importance.

Bone morphogenetic proteins and tissue engineering: future directions.

As long as bone repair and regeneration is considered as a complex clinical condition, the administration of more than one factor involved in fracture healing might be necessary. The effectiveness or not of bone morphogenetic proteins (BMPs) in association with other growth factors and with mesenchymal stem cells in bone regeneration for fracture healing and bone allograft integration is of great interest to the scientific community. In this study we point out possible future developments in BMPs, concerning research and clinical applications.

SPECT/CT with a hybrid imaging system in the study of lower gastrointestinal bleeding with technetium-99m red blood cells.

AIM: Lower gastrointestinal (GI) hemorrhage is a complex clinical problem that requires disciplined evaluation for successful management. This study was conducted to evaluate the applicability of single photon emission computed tomography/computed tomography (SPECT/CT) in patients with acute lower gastrointestinal bleeding undergoing scintigraphy with 99mTc-labelled red blood cells (RBC), and to assess the additional clinical value of fused images when compared to the standard radionuclide scan. METHODS: Twenty-seven patients presenting with acute lower GI tract hemorrhage were studied with conventional dynamic and planar 99mTc-RBC imaging. In 19 patients with positive findings on scans taken within 6 hours, a SPECT/CT study was immediately performed using a hybrid system composed of a dual-head, variable angle gamma camera and an X-ray tube. The number of patients in whom SPECT/CT changed the scintigraphic interpretation with regard to the presence or site of GI blood loss as confirmed by other diagnostic or therapeutical procedures was recorded. RESULTS: Image fusion was easy and successful in all patients showing perfect correspondence between SPECT and CT data and allowing precise anatomical localization of the sites of 99mTc-RBC extravasation. SPECT/CT had significant impact on the scintigraphic results in 7/19 patients (36.8%): in 6 patients it precisely localized the bleeding foci whose location could not be identified in standard scans and in one it excluded the presence of an active GI hemorrhage. CONCLUSIONS: SPECT/CT with a hybrid system is feasible and useful for facilitating imaging interpretation and improving the accuracy of 99mTc-RBC scintigraphy in patients with acute lower GI bleeding.

Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients.

The purpose of this prospective randomised clinical study was to compare the efficacy of recombinant bone morphogenetic protein 7 (rhBMP-7) and platelet-rich plasma (PRP) as bone-stimulating agents in the treatment of persistent fracture non-unions. One hundred and twenty patients were randomised into two treatment groups (group rhBMP-7 vs. group PRP). Sixty patients with sixty fracture non-unions were assigned to each group (median age: 44 years, range 19-65, for the rhBMP-7 group and 41 years, range 21-62, for the PRP group, respectively). In the rhBMP-7 group, there were 15 tibial non-unions, 10 femoral, 15 humeral, 12 ulnar, and 8 radial non-unions. In the PRP group, there were 19 tibial non-unions, 8 femoral, 16 humeral, 8 ulnar, and 9 radial non-unions. The median number of operations performed prior to our intervention was 2 (range 1-5) and 2 (range 1-5) with autologous bone graft being used in 23 and 21 cases for the rhBMP-7 and PRP groups, respectively. Both clinical and radiological union occurred in 52 (86.7%) cases of the rhBMP-7 group compared to 41 (68.3%) cases of the PRP group, with a lower median clinical and radiographic healing time observed in the rhBMP-7 group (3.5 months vs. 4 months and 8 months vs. 9 months, respectively). This study supports the view that in the treatment of persistent long bone non-unions, the application of rhBMP-7 as a bone-stimulating agent is superior compared to that of PRP with regard to their clinical and radiological efficacy.

Identification of 217 unreported mutations in the F8 gene in a group of 1,410 unselected Italian patients with hemophilia A.

To provide a National database, 1,410 unrelated hemophilia A (HA) patients were investigated using screening methods denaturing high-performance liquid chromatography (DHPLC), conformational-sensitive gel electrophoresis (CSGE)] and/or direct sequencing. F8 gene mutations were identified in 877 (81%), 146 (82%), and 133 (89%) families with severe, moderate, or mild HA, respectively. Among the 382 different mutations detected, 217 (57%) have not previously been reported in the F8 Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS) database. Mutations leading to a null allele accounted for 82, 15%, and less than 1% of severe, moderate, or mild HA, respectively. A missense mutation was identified in 16%, 68%, and 81% of severe, moderate, or mild HA, respectively. They included 105 missense mutations (48%), 41 small deletions (19%), 25 splice site mutations (12%), 24 nonsense mutations (11%), 18 insertions (8%), three large deletions (1%), and one deletion plus insertion. Unreported mutations were distributed throughout the F8 gene, as they affected all F8 exons but exon 20. We report a wide spectrum of mutations collected in a large National database. The type of mutation was a strong predictor of the clinical phenotype. This database is expected to considerably improve the genetic counseling and medical care of HA families in Italy.

Genetic diagnosis of haemophilia and other inherited bleeding disorders.

Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is inversely proportional to the degree of factor deficiency. Haemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII) and factor IX (FIX). Together with von Willebrand's disease, a defect of primary haemostasis, these X-linked disorders include 95% to 97% of all the inherited deficiencies of coagulation factors. The remaining defects, generally transmitted as autosomal recessive traits, are rare with prevalence of the presumably homozygous forms in the general population of 1:500,000 for FVII deficiency and 1 in 2 million for prothrombin (FII) and factor XIII (FXIII) deficiency. Molecular characterization, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children affected by coagulation disorders in developing countries, where patients with these deficiencies rarely live beyond childhood and where management is still largely inadequate. These characterizations are possible by direct or indirect genetic analysis of genes involved in these diseases, and the choice of the strategy depends on the effective available budget and facilities to achieve a large benefit. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection. However, in countries with limited facilities and low budget resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article reviews the genetic diagnosis of haemophilia, genetics and inhibitor development, genetics of von Willebrand's disease and of rare bleeding disorders.

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

AIMS: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. CASE HISTORY: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). CONCLUSION: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

Peripheral quantitative Computed Tomography (PQCT) in the evaluation of bone geometry, biomechanics and mineral density in postmenopausal women.

AIM: Non-invasive assessment of bone geometry, biomechanics, and mineral content in postmenopausal women by peripheral quantitative Computed Tomography (pQCT). MATERIAL AND METHODS: Total, trabecular and cortical mineral density (totBMD, cortBMD, trabBMD), and the geometrical (total area, trabecular area, cortical area) and biomechanical properties of bone (strength-strain index, cortical thickness) were assessed in 93 consecutive post-menopausal women (mean age: 63+/-7 yrs; age at menopause: 49+/-6 yrs; years since menopause: 14+/-9 yrs) by pQCT at the ultradistal radius of non-dominant forearm. RESULTS: Compared with 50 healthy women at peak of bone mass, volumetric total, trabecular and cortical bone densities were significantly reduced in postmenopausal subjects (TotBMD: 318+/-106 mg/cm3 vs ctr 442+/-100, -28%, p<0.001; TrabBMD: 117+/-59 mg/cm3 vs ctr: 203+/-47, -42%, p<0.001; CorBMD: 764+/-159 mg/cm3 vs 921+/-111, -17%, p<0.001). The bone loss was greater in trabecular bone. Cortical area (0.7+/-0,1 cm2 vs ctr: 0.8+/-0.1, -12.5%, p<0.001), cortical thickness (0.151+/-0.02 cm vs ctr: 0.169+/-0.03, -11%, p<0.001), and strength-strain index (686+/-207 mm3 vs ctr: 883+/-165, -22%, p<0.001) were significantly lower in post-menopausal women in comparison with the controls. Years since menopause and age showed a significant negative correlation with bone mineral densities and biomechanical parameters. CONCLUSIONS: In post-menopausal women pQCT showed: 1) osteopoenia in all bone compartments, greater at the trabecular level, related to age and years since menopause; 2) reduced cortical density and cortical thickness, consistent with a reduced ability of bone to absorb loading forces; 3) reduced strength-strain index, indicative of inability to adapt to mechanical use and augmented risk for fracture. We conclude that pQCT is a valuable tool for measuring the true volumetric mineral density and the geometrical and biomechanical indexes of bone, which could be proposed in current clinical practice for the assessment of osteoporosis.

Post-stress end-systolic left ventricular dilation: a marker of endocardial post-ischemic stunning.

Several studies have shown the accuracy of gated single photon emission computed tomography (SPECT) using thallium-201 and technetium tracers in the assessment of myocardial perfusion and function. Gated SPECT has been successfully utilized to detect post-stress left ventricular ejection fraction (LVEF) reduction resulting from post-ischemic stunning in patients with coronary obstruction. The aim of this study was to evaluate whether the post-stress LVEF impairment could be related to the post-stress end-systolic ventricular dilation resulting from post-ischemic endocardial stunning. Two hundred and eighty-two consecutive patients were studied by conventional diagnostic 2 day stress/rest gated SPECT following injection of 925 MBq of 99mTc-tetrofosmin using a dual-headed SPECT camera. One hundred and forty-seven of these patients (52%) showed reversible perfusion defects, 69 (24%) permanent defects and the remaining 66 (24%) had normal perfusion. One hundred and thirty-eight of these patients had a history of myocardial infarction (MI) and 19% underwent coronary angiography without an intervening cardiac event. Perfusion was analysed on ungated images using 20 segments scored on a five-point scale (0, normal; 4, no uptake), while wall thickening (WT) was assessed visually on stress/rest end-systolic images using a four-point score (0, normal; 3, absence of WT). LVEF and volumes were calculated using an automatic algorithm. The post-stress and rest ratios were determined for both end-diastolic (EDV) and end-systolic (ESV) volume. Normal values for all these parameters were obtained using data from 149 patients with a low likelihood (<5%) of coronary artery disease (CAD). In 50 of the 147 (34%) of patients with reversible perfusion defects, post-stress LVEF was >5% lower than rest values (stunned group), while the remaining 97 patients did not show a significant LVEF change (group 2A). The percentage of patients who developed exercise-induced angina, the percentage of patients who underwent coronary angiography and the segmental summed perfusion and WT scores were significantly higher in the stunned group compared with group 2A. Only ESV increased significantly post-stress, and this increase occurred only in stunned patients. Both EDV and ESV ratios were significantly higher in the stunned group compared with normal controls (P=0.008 and P<0.000001, respectively) and with the subgroup 2A (P=0.011 and P<10(-12), respectively). The ESV stress/rest ratio correlated significantly with the summed WT difference score by univariate analysis in stunned patients. It can be concluded that the post-stress ESV dilation, obtained by stress/rest gated SPECT, seems to be due to endocardial post-ischemic stunning. The stunned patients showed more severe clinical, angiographic, perfusion and function parameters.

Inflammatory bowel diseases are not associated with major hereditary conditions predisposing to thrombosis.

Patients with inflammatory bowel diseases (IBD) are at increased risk for thromboembolic complications. Our aim was to evaluate whether the increased risk for thrombosis in IBD could be due to a genetic association of IBD with hereditary prothrombotic conditions. In all, 102 IBD patients (51 with ulcerative colitis and 51 with Crohn's disease) with no history of thrombosis and 204 matched normal subjects were enrolled. DNA specimens were evaluated by PCR and restriction fragment length polymorphism for factor V Leiden, methylene tetrahydrofolate reductase (MTHFR) and prothrombin gene mutations. In IBD patients and matched controls the observed allele frequencies were similar, being 1.5% and 1.2% for factor V Leiden gene mutation, 1.1% and 0.7% for prothrombin gene mutation, and 45.1% and 47.4% for MTHFR gene mutation, respectively. These rates also were not significantly different when patients were analyzed according to age and sex distribution, diagnosis, and extension and clinical type of disease. In conclusion, our study shows no association between IBD and the most frequent hereditary prothrombotic conditions. Other factors should be evaluated in order to understand the mechanisms underlying the thrombotic risk of IBD.

[Osteoporosis and phytoestrogens: an assessment of bone mineral density via quantitative peripheral computed tomography in milk-egg-vegetarian women in the premenopause]. / Osteoporosi e fitoestrogeni: valutazione della densità minerale ossea mediante Tomografia Computerizzata quantitativa periferica nelle donne lattoovovegetariane nella premenopausa.

PURPOSE: Noninvasive assessment of bone mineral density, geometrical and biomechanical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with "Mediterranean" dietary intake lacking in these substances. MATERIAL AND METHODS: Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated in 15 female subjects with phytoestrogens dietary intake. Peripheral quantitative Computed Tomography (pQCT) was used to make measurements at the distal radius of the nondominant forearm. Fifteen age-matched subjects with "Mediterranean" dietary intake were chosen as a control group. Cross-sectional area (Total A), trabecular area (TA), cortical area (CA), cortical thickness (CThk) and strength strain index (SSI) were assessed as biomechanical parameters. RESULTS: Daily consumption of phytoestrogens was significatively different in the two groups (phy: 17.45 mg/die vs ctr: 0.35; p < 0.0005), while calcium intake was similar (phy: 652 mg/die vs ctr: 650). Total (0.460 g/cm3 vs ctr: 0.433) and trabecular (phy: 0.209 g/cm3 vs ctr: 0.189) bone mineral densities, such as SSI (phy: 925 mm3 vs ctr: 894) values, were higher in women with dietary intake of phytoestrogens, in comparison with the relative controls, but not significantly (p = ns). Among geometrical parameters, total area and cortical area were tendential in women with a vegetarian diet while cortical thickness was the same in both groups. CONCLUSIONS: pQCT showed higher bone mineral density (total and trabecular) and SSI values in premenopausal women with dietary intake of phytoestrogens. Despite the lack of statistical significance, these preliminary results, should further support the few literature findings about the potential role of phytoestrogens consumption in preventing trabecular bone loss. However, further studies are warranted to evaluate definitively the efficacy of phytoestrogens in preventing postmenopausal osteoporosis.

Effects of infusion of glucose-insulin-potassium on myocardial function after a recent myocardial infarction.

UNLABELLED: We studied the effects of glucose, insulin, and KCl infusion (GIK), on regional myocardial perfusion and function by 99m-Tc-tetrofosmin-gated SPECT. METHODS: We studied 21 male patients with their first uncomplicated acute myocardial infarction (AMI). All patients underwent a rest and submaximal stress before and after 24-hour infusion of GIK-solution (group A) or saline solution (group B). RESULTS: Group A showed better stress tolerance and ischaemic threshold improvement after GIK infusion whilst no statistical differences were found between basal and post-infusion test in group B. At first the stress test in group A, of the 192 segments analysed, 52 (27%) showed reversible perfusion defect. In group B, of 144 segments analysed, 31 (21%) showed reversible perfusion defect. A post-infusion analysis in group A showed a post-GIK end-diastolic significant count improvement in 21 segments, and a post-GIK end-systolic count improvement in 22 segments. In group B, perfusion increase was observed only in 4 segments, whilst systolic thickening increase was observed only in 1 segment. CONCLUSION: These data demonstrate the efficacy of GIK infusion to improve regional myocardial perfusion and function mainly in segments adjacent to the recently infarcted area.