An observational study of inhaled-treprostinil respiratory-related safety in patients with pulmonary arterial hypertension.

Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory-related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory-related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)-approved PAH therapies. This was a long-term, prospective, observational study. All respiratory-related AEs were recorded during the study. The number of PAH patients enrolled was 1,333, 666 treated with inhaled treprostinil and 667 controls (treated with an FDA-approved PAH therapy other than inhaled treprostinil), for a total of 958 and 1,094 patient-years of exposure, respectively. In the inhaled-treprostinil group, 1,281 respiratory-related AEs were reported in 403 patients (61%), and in the control group, 1,295 respiratory-related AEs were reported in 388 patients (58%). Cough, throat irritation, nasal discomfort, and hemoptysis were the most common respiratory-related AEs (occurring in ≥2% of patients in either treatment group) that demonstrated a higher number of events per patient-year of exposure in the inhaled-treprostinil group than in the control group (risk ratio [95% confidence interval]: 1.487 [1.172-1.887], 3.777 [2.050-6.956], 2.039 [1.072-3.879], and 1.957 [1.024-3.741], respectively). Overall, inhaled treprostinil was well tolerated by PAH patients in routine clinical care, with respiratory-related AEs consistent with the known safety profile (trial registration: clinicaltrials.gov identifier: NCT01266265).

A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in graves' ophtalmopathy patients with different clinical activity score.

The present study describes the preliminary results of the use of 99mTc-anti-TNF-α scintigraphy as a new diagnostic approach to evaluate patients presenting with Graves' ophthalmopathy (GO). Patients (n=25) presenting at different inflammatory stages of GO and 10 healthy volunteers underwent 99mTc-anti-TNF-α scintigraphy. Images were obtained 15 min after the intravenous injection of 370 MBq (10 mCi) 99mTc-anti-TNF-α. Planar images were obtained in a 256×256 matrix (each lasting 5 min) and single photon emission computed tomography (SPECT) scan lasting 13 min. Regions of interest (ROI) were drawn on the orbit and cerebral hemispheres. The uptake of 99m Tc-anti-TNF-α in these regions was compared and positive scintigraphy established when the ROI was >2.5. In addition, uptake for each positive exam was scored as either slight (2.6-5.1), moderate (5.2-7.6), or high (>7.6). In this pilot study, 69 orbits were evaluated (1 patient had only 1 eye), and 27 had a positive CAS (≥3/7). Scintigraphies were positive in 38 orbits. Comparing the results of the exams with CAS, a high sensitivity and negative predictive values were determined for scintigraphy (96.3% and 96.7%, respectively). However, the specificity and the positive predictive values were 71.4% and 68.4%, respectively, with an accuracy of 81.2%. The exclusion of examinations that were slightly positive from the analysis resulted in an improvement in test accuracy (95.5%). The preliminary results suggest that 99mTc-anti-TNF-α scintigraphy is a promising procedure for the evaluation of active orbital inflammation in GO.

9°Yttrium-hydroxyapatite: a new therapeutic option for radioactive synovectomy in haemophilic synovitis.

Recurrent haemarthroses often lead to chronic synovitis in patients with haemophilia and von Willebrand disease. Radioactive synovectomy with yttrium-90 (9°Y) citrate is frequently used to treat this complication, usually with good results. Since 2006, the Nuclear Energy Research Institute (IPEN, Sao Paulo, Brazil) has produced hydroxyapatite particles labelled with 9°Y for radioactive synovectomy. The aim of this study was to compare the results achieved by both forms of 9°Y in the treatment of haemophilic synovitis. We included 221 joints from 136 patients (age range: 6-20 years), treated by one of the two radiopharmaceuticals, at the Hemocenter of Mato Grosso, Brazil. The outcomes analysed were the annual frequency of haemarthrosis, articular pain and joint range of motion before and 1 year after RS. Similar results were achieved regardless of whether 9°Y hydroxyapatite or 9°Y citrate was used, and results were independent of the joint type, age, gender, radiologic stage and presence of inhibitors. 9°Y hydroxyapatite appears to be equivalent to the reference product 9°Y citrate in the treatment of chronic synovitis associated with bleeding disorders.

Monitoring rheumatoid arthritis synovitis with 99mTc-anti-CD3.

The aim of this study was to investigate the feasibility of using a monoclonal antibody (OKT3) labelled with technetium-99m (99mTc) to monitor disease activity in patients with rheumatoid arthritis. We evaluated 38 patients who were diagnosed with rheumatoid arthritis and classified as Classes II and III after functional assessment (according to the revised criteria specified by the American College of Rheumatology). Two sets of planar anterior images of the patients' wrists, metacarpophalangeal and interphalangeal joints, elbows, shoulders and knees joints were obtained 1 h and 3 h after the injection of 99mTc-OKT3. The scintigraphic findings showed significant correlation (p<0.05) between the radiopharmaceutical accumulation of 99mTc-OKT3 and swollen joints, tender joints and the visual analogue scale. They were able to differentiate patients in remission from patients with active synovitis, according to DAS 28. In contrast, there was no correlation between the radiopharmaceutical accumulation and the patients' age, gender, duration of disease or erythrocyte sedimentation rate. A relatively high disease activity score of 28 joints (4.08+/-1.74) was found in the majority of patients. In conclusion, 99mTc-OKT3 scintigraphy is a reliable and objective method for detecting synovial activity, and can be used to observe disease prognosis.

Use of 99mTc-mononuclear leukocyte scintigraphy in nosocomial fever.

PURPOSE: To determine the overall diagnostic accuracy of mononuclear leukocyte- 99mTc scintigraphy in the routine detection of infectious lesions and fever of unknown origin (FUO) in inpatients. MATERIAL AND METHODS: The use of mononuclear leukocyte 99mTc scintigraphy is presented in 87 patients who fulfilled the Durack and Street diagnostic criteria of nosocomial FUO; 66 patients were suspected of having infectious lesions (myocarditis, endocarditis, infected catheters, diabetic foot, and osteomyelitis) and 21 patients presented with unknown causes of FUO. Scans were carried out 1, 3, and 24 h after injection of labeled leukocytes. RESULTS: In three cases (3/27) where scintigraphs were negative, biopsies were positive. There were two (2/87) false-positive scintigrams. We found a 95.8% sensitivity and 92.3% specificity. PPV was 93.8%, PPN 94.7%, and accuracy 94.2%. CONCLUSION: Mononuclear leukocyte 99mTc scintigraphy showed high sensitivity, specificity, positive and negative predictive values in patients with nosocomial FUO. These results suggest an important role for nuclear medicine in the management of patients with infection/inflammation.

Identification of sentinel node in breast cancer: comparison between peritumoral and periareolar injection of the radiopharmaceutical contrast medium.

Axillary node status is the most important prognostic factor for patients with primary breast carcinoma. The sentinel node biopsy (SN) technique has received much attention as a possible alternative to axillary lymph node dissection. The aim of this study is to identify the sentinel node by periareolar and subdermal injection of the radiopharmaceutical in four points, independent of tumor topography and the presence of biopsies and/or previous surgery. The peritumoral injection technique was carried out for comparison purposes. This study was performed on 115 patients, divided into 2 groups: Group A (25 patients, peritumoral injection) and Group B (90 patients, injection in four points). All the SN biopsies were studied by both imprint cytology and H&E staining. Control axillary lymph-node dissection was followed in all patients from Group A and in these positive cases from Group B. Twenty-two out of the twenty-five (88%) SNs were identified in Group A. There was no false negative; the sensitivity and specificity were 100%. Eighty-two of the ninety (91.1%) SNs were identified in Group B. Lymphoscintigraphy showed radiopharmaceutical migration to axilla in 93.7% of the cases. Hotspot area was 10 to 100 times the intensity of the background radiation. Among the 92 cases with negative sentinel nodes at intraoperative examination (TP), the SN histopathology confirmed the absence of cancer cells in 89 patients, whereas 3 were positive for metastatic cells. This study shows that periareolar injection in four points seems to be a good lymphatic mapping method for SN identification. We suggest standardizing this site of injection to identify the SNs. More studies to confirm these findings are ongoing.

Diagnosis of renal allograft rejection and acute tubular necrosis by 99mTc-mononuclear leukocyte imaging.

One hundred kidney transplant recipients were evaluated on the first and fifth days after transplantation by Tc-99m mononuclear cell scintigraphy. We have developed a quantitative method to diagnose rejection and acute tubular necrosis (ATN) by comparing regions of interest drawn on allograft scintigraphs at different times after endovenous administration of the labeled cells. We suggest that the use of Tc-99m-WBC may be useful for the early diagnosis of rejection and the differential diagnosis of ATN.