[18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia.

PURPOSE: This study aims to identify in patients with neuroendocrine neoplasia (NEN) the potential correlation between FDG-PET findings and responses to everolimus therapy to identify predictors of long-term efficacy. METHODS: Retrospective analysis of patients with sporadic, advanced, progressive NEN treated with everolimus was performed based on the available data on FDG-PET patients obtained before commencing therapy. Data are expressed as the median (25-75th IQR). Risk factor analysis and survival analysis were performed by logistic regression and Cox proportional hazard regression and the determination of Kaplan-Meier curves, as appropriate. RESULTS: Sixty-six patients were evaluated (NET G1 19.7%, NET G2 75.7%, and NET G3 4.6%), including 45.4% with positive FDG-PET findings. Overall, disease stabilization and a partial response were achieved for 71.2% and 6% of patients, respectively. A long-term response (> 24 months) was observed in 33% of patients. Ki67 was the only predictor of tumor progression (p = 0.03). No significant difference in clinical outcomes was observed between patients with positive or negative FDG-PET findings (median PFS was 24 months and 18 months, respectively, p = 0.337; the disease control rate was 83.3% and 70%, respectively, p = 0.245). CONCLUSIONS: Everolimus is a valid therapeutic option for advanced, progressive, well-differentiated NEN, even in patients with positive FDG-PET findings.

Labelling and Clinical Performance of Human Leukocytes Labelled with 99mTc-HMPAO Using Leukokit® with Gelofusine versus Leukokit® with HES as Sedimentation Agent.

The scintigraphy with radiolabelled autologous leukocytes (WBCs) is considered the gold-standard technique for imaging infections. Leukokit® is a commercially available, disposable, sterile kit for labelling WBCs ex vivo. In this kit, WBCs isolation from red blood cells (RBCs) was performed using poly(O-2-hydroxyethyl)starch (HES) as the RBCs sedimentation agent. Due to its poor availability, HES has been recently replaced by Gelofusine as the RBC sedimentation agent. The aim of this study was to compare the labelling efficiency and the diagnostic accuracy of WBCs labelled with Leukokit® with HES vs Leukokit® with Gelofusine. WBCs were isolated using HES or Gelofusine for 45 minutes and then purified from platelets (PLTs) and labelled with 1.1 ± 0.3 GBq of freshly prepared 99mTc-HMPAO. The following parameters were evaluated: the number and type of recovered WBCs, RBCs contamination, PLTs contamination, vitality of neutrophils, and chemotactic properties of neutrophils. Clinical comparison was performed between 80 patients (33 males; age 67.5 ± 14.2) injected with 99mTc-HMPAO-WBCs, using HES as the sedimentation agent, and 92 patients (38 males; age 68.2 ± 12.8) injected with 99mTc-HMPAO-WBCs using Gelofusine as the sedimentation agent. Patients were affected by prosthetic joint infections, peripheral bone osteomyelitis, or vascular graft infection. We compared radiolabelling efficiency (LE), final recovery yield (RY), and diagnostic outcome based on microbiology or 2-year follow-up. Results showed that HES provides the lowest RBCs and PLTs contamination, but Gelofusine provides the highest WBC recovery. Both agents did not influence the chemotactic properties of WBCs, and no differences were found in terms of LE and RY. Sensitivity, specificity, and accuracy were also not significantly different for WBCs labelled with both agents (diagnostic accuracy 90.9%, CI = 74.9-96.1 vs 98.3%, CI = 90.8-100, for HES and Gelofusine, respectively). In conclusion, Gelofusine can be considered a suitable alternative of HES for WBCs separation and labelling.

A computational fluid dynamics analysis of the effects of size and shape of anterior nasal septal perforations.

BACKGROUND: Nasal septal perforations (NSPs) often cause bleeding, crusting, obstruction, and/or whistling. The objective was to analyze the impact of anterior NSP size and shape on nasal physiology using computational fluid dynamics (CFD). METHODS: A 3-dimensional model of the nasal cavity was constructed from a radiologically normal CT scan using imaging software. Anterior NSPs (ovoid (ONSP): 0.5, 1, 2, and 3 cm long anterior-to-posteriorly and round (RNSP, 0.5 and 1 cm)) were virtually created in the model and divided into ventral, dorsal, anterior, and posterior regions. Steady-state inspiratory airflow, heat, and water vapor transport were simulated using Fluent CFD software. Air crossover through the perforation, wall shear, heat flux, water vapor flux, resistance, and humidification were analyzed. RESULTS: Air crossover and wall shear increased with perforation size. Regionally, wall shear and heat and water vapor flux were highest posteriorly and lowest anteriorly, generally increasing with size in those regions. RNSPs had greater heat and water vapor flux compared to corresponding size ONSPs. Resistance decreased by 10% or more from normal only in the 3 cm ONSP. Maximum water content was achieved more posteriorly in larger NSP nasal cavities. CONCLUSIONS: High wall shear and heat and water vapor flux in posterior perforation regions may explain the crusting most commonly noted on posterior NSP edges. This preliminary study suggests that larger NSPs have a greater effect on nasal resistance and water content. Decrease in resistance with larger NSP size may be implicated in reported symptomatic improvement following enlargement of NSPs for treatment.

Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells.

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20-40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.

Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline.

INTRODUCTION: Radiolabelled autologous white blood cells (WBC) scintigraphy is being standardized all over the world to ensure high quality, specificity and reproducibility. Similarly, in many European countries radiolabelled anti-granulocyte antibodies (anti-G-mAb) are used instead of WBC with high diagnostic accuracy. The EANM Inflammation & Infection Committee is deeply involved in this process of standardization as a primary goal of the group. AIM: The main aim of this guideline is to support and promote good clinical practice despite the complex environment of a national health care system with its ethical, economic and legal aspects that must also be taken into consideration. METHOD: After the standardization of the WBC labelling procedure (already published), a group of experts from the EANM Infection & Inflammation Committee developed and validated these guidelines based on published evidences. RESULTS: Here we describe image acquisition protocols, image display procedures and image analyses as well as image interpretation criteria for the use of radiolabelled WBC and monoclonal antigranulocyte antibodies. Clinical application for WBC and anti-G-mAb scintigraphy is also described. CONCLUSIONS: These guidelines should be applied by all nuclear medicine centers in favor of a highly reproducible standardized practice.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjögren's syndrome treated with Infliximab: a pilot study.

BACKGROUND: Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue ((99m)Tc-EDDA/tricine-HYNIC-tyr(3)-octreotide ((99m)Tc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjögren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment. METHODS: Eighteen patients with rheumatoid arthritis and secondary Sjögren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-α. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of (99m)Tc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively. RESULTS: All patients showed uptake of (99m)Tc-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands. CONCLUSIONS: SRS using (99m)Tc-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjögren's syndrome. It may also aid therapy decision-making with anti-TNFα antibodies in the joints but not in salivary glands.

Current status of PET imaging of differentiated thyroid cancer with second generation radiopharmaceuticals.

Although the prognosis of differentiated thyroid cancer (DTC) is favorable, some histotypes show worst clinical outcome and higher risk of recurrence. Serum thyroglobulin (Tg) levels and 131I-whole-body-scan (WBS), together with neck ultrasound (US), represent the golden standard for DTC follow-up. Nevertheless, the relatively high frequency of patients with high Tg levels and negative WBS requires further investigations by using new imaging modalities. The availability of whole body positron emission tomography (PET) methods, in parallel with the advances in radiochemistry, offer a wide substrate for many solutions. To this day ¹8F-fluoro-deoxy-glucose (¹8F-FDG) PET/CT still represents the imaging of choice in follow-up of patients with high serum Tg and negative ¹³¹I-WBS but in the last decades the research has focused on finding "second generation" radiopharmaceuticals for PET imaging, with both diagnostic and prognostic purposes, aiming to change the way to image thyroid cancer. Moreover, the use of various PET radiopharmaceuticals, that offer the possibility to explore different pathways involved in thyroid cancer, could find important applications in the near future for clinical decision making in order to program tailored treatments and follow-up. It would be desirable to use the same radiopharmaceutical for both imaging and dosimetric purpose to achieve a tailored therapy. Many efforts are focused in this direction and ¹²4I-PET/CT is now emerging as a valid tool in restaging and therapy management of DTC with promising results. Although the preliminary data available in literature require a confirmation in larger studies with longer follow-up, we think that in next future ¹²4I-PET/CT could gain an important role for management of DTC. The aim of this review was to perform a systematic analysis of literature describing the state of art of "second generation" PET-radiopharmaceuticals for imaging DTC. Discussion is focused on the utility of ¹²4I-PET/CT, but we also mention the pathways explored by 68Gallium-somatostatin analogues, ¹8F-FLT and ¹¹C-MET and their applications in this clinical setting.

New approaches to image thyroid cancer cells and microenvironment.

Poorly differentiated thyroid cancer (PDTC) and undifferentiated thyroid cancer (UDTC) are still life-threatening pathologies, because of the lack of well-established diagnostic and therapeutic approaches. In the past, many attempts have been made to develop radiopharmaceutical to diagnose or treat radioactive iodine (RAI)-refractory metastases or recurrences, with limited results. Indeed, it was not possible to find a specific and overexpressed marker to be used as target of radiopharmaceuticals or targeted therapies. Nowadays, with novel advances in the field of tumor microenvironment, many new markers are available to be used as suitable targets for targeted therapies interfering with signalling pathways of cells involved in the mechanisms that favour tumor growth and metastatization. This opened new perspective in the use of radiopharmaceuticals targeting components of tumor microenvironment for early diagnosis, pre-operative staging or therapy planning and follow up with targeted drugs. In the present review we present the state of novel approaches to image thyroid cancer and its microenvironment, focusing on RAI-refractory thyroid cancer as a real clinical problem to be solved.

Imaging T-lymphocytes in inflammatory diseases: a nuclear medicine approach.

Increasing interest and research efforts have been made in search of specific radiolabelled probes for imaging different immune cells (including T-lymphocytes) in inflammation and infection. This has led to early detection of lymphocyte infiltration, and the deepening of our understanding of pathogenesis of immune mediated diseases. In-vivo imaging of T-lymphocytes with radiolabelled specific probes may provide an important piece of information about inflammatory lesions, which could be very important to understand the molecular mechanism of action of any drug and/or their effect on the microenvironment of the immune system of the body. The present review focuses on radiolabelled T-lymphocytes and different monoclonal antibodies, peptides, cytokines, chemokine used for scintigraphic imaging of T-lymphocytes and their subsets.

Diagnostic flowcharts in osteomyelitis, spondylodiscitis and prosthetic joint infection.

Infections of the bone, spine and prosthetic joints are serious and complex conditions to diagnose and to treat. Structured diagnostic workup may very well improve the accuracy and speed of diagnosis, thereby improving the outcome since treatment may very well be more successful and less harmful if timely management is started. Literature shows no uniform advise on diagnosis. The EANM organized a consensus meeting with representatives from the involved disciplines in order to develop common flowcharts for the diagnosis of osteomyelitis, spondylodiscitis and prosthetic joint infections. In this report the proceedings of this consensus meeting, including the proposed flowcharts for diagnosis, are published.

High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients?

Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,<0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p<0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.

Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines.

The management of patients with IBD requires evaluation with objective tools, both at the time of diagnosis and throughout the course of the disease, to determine the location, extension, activity and severity of inflammatory lesions, as well as, the potential existence of complications. Whereas endoscopy is a well-established and uniformly performed diagnostic examination, the implementation of radiologic techniques for assessment of IBD is still heterogeneous; variations in technical aspects and the degrees of experience and preferences exist across countries in Europe. ECCO and ESGAR scientific societies jointly elaborated a consensus to establish standards for imaging in IBD using magnetic resonance imaging, computed tomography, ultrasonography, and including also other radiologic procedures such as conventional radiology or nuclear medicine examinations for different clinical situations that include general principles, upper GI tract, colon and rectum, perineum, liver and biliary tract, emergency situation, and the postoperative setting. The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas such as the comparison of diagnostic accuracy between different techniques, the value for therapeutic monitoring, and the prognostic implications of particular findings.

Radiolabelled white blood cell scintigraphy in the work-up of dermal filler complications.

PURPOSE: Scintigraphy with radiolabelled autologous white blood cells (WBC) is a widely used method for the detection of sites of infection. In this study we evaluated the role of WBC scintigraphy in the diagnosis and follow-up of patients with suspected soft tissue infection caused by dermal fillers in the face. We compared several qualitative and quantitative interpretation criteria and the results obtained with MRI and high-frequency US (HFUS). METHODS: Between 2007 and 2011, ten consecutive patients (all women) aged between 25 and 65 years showing a reaction to dermal fillers were enrolled in the study. In five of these patients WBC scintigraphy was repeated at the end of therapy. Scintigraphy with (99m)Tc-HMPAO-labelled WBC was performed in each patient acquiring planar and SPECT images at 3 h and 20 h as well as HFUS with Doppler analysis and MRI with Gd-DTPA. The final diagnosis was determined by fine-needle aspiration and microbiological analysis of lesions in eight patients (before therapy in six and after therapy in two) and by clinical data and follow-up (at least 1 year) in seven patients (before therapy in four and after therapy in three). Two patients were treated with steroids, and the others were treated with antibiotics for 3 weeks. Several qualitative and semiquantitative interpretation criteria were applied to define the best strategy for accurate diagnosis of infections, implemented by SPECT images in patients with doubtful planar scans. The WBC scintigraphy results were also compared with the MRI and HFUS results. RESULTS: Sensitivity, specificity and accuracy were respectively 90 %, 100 % and 93.3 % for WBC scintigraphy with qualitative and semiquantitative interpretation of planar images and 100 %, 100 % and 100 % with qualitative analysis of SPECT images. Sensitivity, specificity and accuracy for HFUS were 44 %, 66 % and 50 %, and for MRI were 50 %, 100 % and 67.6 %, respectively. Scans performed after therapy in five patients were negative in three and still positive in two (all true results). CONCLUSION: In conclusion, scintigraphy with radiolabelled WBC was found to be the most accurate method for diagnosing infection in patients with long-term dermal filler complications, particularly using qualitative analysis of SPECT images. No differences were observed with planar images using either qualitative or semiquantitative analysis. HFUS and MRI may provide additional important information for defining the nature of the filler and for surgery, but are not accurate enough for diagnosing infection.

Development and testing of a new disposable sterile device for labelling white blood cells.

AIM: White blood cell (WBC) labelling requires isolation of cells from patient's blood under sterile conditions using sterile materials, buffers and disposables under good manufacturing practice (GMP) conditions. Till now, this limited the use of white blood cell scintigraphy (WBC-S) only to well equipped laboratories with trained personnel. We invented, developed and tested a disposable, sterile, closed device for blood manipulation, WBC purification and radionuclide labelling without exposing patient's blood and the operator to contamination risks. This device prototype and a final industrialized device (Leukokit®) were tested for WBC labelling and compared to standard procedure. Leukokit® was also tested in an international multi-centre study for easiness of WBC purification and labelling. METHODS: On the device prototype we tested in parallel, with blood samples from 7 volunteers, the labelling procedure compared to the standard procedure of the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol with respect to cell recovery, labelling efficiency (LE), cell viability (Trypan Blue test) and sterility (haemoculture). On the final Leukokit® we tested the biocompatibility of all components, and again the LE, erythro-sedimentation rate, cell viability, sterility and apyrogenicity. ACD-A, HES and PBS provided by Leukokit® were also compared to Heparin, Dextran and autologous plasma, respectively. In 4 samples, we tested the chemotactic activity of purified WBC against 1 mg/ml of lipopolysaccharide (LPS) and chemotaxis of 99mTc-HMPAO-labelled WBC (925 MBq) was compared to that of unlabelled cells. For the multi-centre study, 70 labellings were performed with the Leukokit® by 9 expert operators and 3 beginners from five centers using blood from both patients and volunteers. Finally, Media-Fill tests were performed by 3 operators on two different days (11 procedures) by replacing blood and kit reagents with bacterial culture media (Tryptic Soy Broth) and testing sterility of aliquots of the medium at the end of procedure. RESULTS: Tests performed with the prototype showed no significant differences with the standard procedure but a faster and safer approach. Tests performed with the final Leukokit® confirmed full biocompatibility, sterility and apyrogenicity of all reagents and plastic ware. Average WBC recovery with Leukokit® was comparable to that of the ISORBE protocol (117x106±24x106 vs. 132x106±29x106 cells, P=not significant). No differences in red blood cells and platelet content were observed. LE was 82% ± 3% for Leukokit® and 65±5% for control (P=0.0003) being PBS vs autologous plasma the main reason of such difference. Cell viability was always >99.9% in both conditions. Chemotactic tests showed no differences between all Leukokit® samples and controls. Haemocultures and Media-Fill tests were always sterile. The procedure was well accepted by expert operators and beginners, with a very fast learning curve (confidence after 2±2 labellings). CONCLUSION: The invented device offers high level of protection to operators and patients. The derived Leukokit® is safe and easy to use, and gives a high LE of WBC without affecting cell viability and function. Being a registered closed, sterile medical device, it may allow easier and faster WBC labelling that is not limited to only well equipped laboratories. Also simultaneously labelling of multiple patients is possible.

Lingual frenectomy: functional evaluation and new therapeutical approach.

AIM: When ankyloglossia is relatively severe and generates mechanical limitations and functional challenges, surgical reduction of the frenum is indicated. MATERIALS AND METHODS: Laser technique is an innovative, safe and effective therapy for frenectomy in both children and adolescents. Erbium:YAG laser (2940nm) can be useful for paediatric dentist: 1.5W at 20pps is a commonly used average power to easily, safely and quickly cut the frenum. RESULTS: Usually after laser frenectomy, the postoperative symptoms and relapse are absent. CONCLUSION: Early intervention is advisable to reduce the onset of alterations correlated to the ankyloglossia. A multidisciplinary approach to the problem is advisable, in collaboration with orthodontist, physiotherapist and speech therapist, to better resolve the problem.

Role of scintigraphy with 99mTc-infliximab in predicting the response of intraarticular infliximab treatment in patients with refractory monoarthritis.

PURPOSE: The rationale for the present study was to evaluate the predictive role of (99m)Tc-infliximab scintigraphy in therapy decision-making in patients with refractory monoarthritis and also candidates for intraarticular (IA) infliximab treatment. METHODS: We studied 12 patients (5 with rheumatoid arthritis and 7 with spondyloarthropathy) with active monoarthritis (11 knees and 1 ankle) that had lasted for at least 3 months. Patients were evaluated clinically and ultrasonographically at baseline and 12 weeks after IA administration of infliximab. At the same time-points, (99m)Tc-infliximab scintigraphy was performed: planar anterior and posterior images of arthritic joints were acquired at 6 and 20 h after injection and target-to-background (T/B) ratios were calculated. RESULTS: After treatment, a significant improvement in clinical and ultrasonographic parameters was recorded in six patients. Three patients had a partial response and three did not respond. Regarding scintigraphic evaluation, the T/B ratio analysis showed a significantly higher uptake in affected than in nonaffected joints before therapy (1.78 ± 0.46 vs. 1.29 ± 0.27, p = 0.006 at 6 h; 2.05 ± 0.50 vs. 1.41 ± 0.36 at 20 h, p = 0.002), and mean uptake at 20 h was also significantly higher than at 6 h (p = 0.0004). Scintigraphy showed a significant decrease in posttherapy T/B ratios of the affected joints (p = 0.0001 at 6 h and p = 0.0001 at 20 h), indicating a reduction in TNF into the affected joints. Most importantly, responders showed a significantly higher percentage increase in pretherapy uptake from 6 h to 20 h in the affected joints than nonresponders (p = 0.00001). CONCLUSION: The results of the present investigation suggest that (99m)Tc-infliximab scintigraphy could be a useful tool to predict the clinical response to IA infliximab treatment in patients with refractory monoarthritis.