A retrospective analysis of the accuracy of radioactively labeled autologous leukocytes in patients with infected prosthetic joints

BACKGROUND: Labeled leukocyte scintigraphy (LS) is considered a valuable tool in preoperative diagnosis of prosthetic joint infections (PJI). The aim of this study was to determine the accuracy of LS combined with bone marrow scintigraphy (BMS), as well as inflammation markers CRP and WBC, in detecting infection in patients with prosthetic joints. MATERIAL AND METHODS: This study included patients suspected of having PJI between January and September 2013 at the Vienna General Hospital who underwent imaging with 99mTc-HMPAO labeled autologous leukocytes and subsequent BMS. Diagnostic accuracy was assessed in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 48 patients were included. The most common joint investigated was knee (25), followed by hip (9), shoulder (2), and elbow (1). Other parts of the body investigated included the femur (6), tibia (2), leg (2), and foot (1). The pathogens most frequently isolated included Staphylococcus epidermidis and Candida albicans. The sensitivity of LS was 60%, specificity 97%, PPV 86% and NPV 90%. Overall accuracy was calculated to be 90%. CONCLUSIONS: This study was able to demonstrate that 99mTc-HMPAO labeled autologous leukocytes in patients presenting with symptoms of PJI is accurate. In contrast, however, inflammation markers CRP and WBC are not accurate pre-diagnostic markers for PJI

TP53 is not a prognostic markerâ clinical consequences of a generally disregarded fact

Technological progress within the last 15â 20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the â tripleâ R principleâ : robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.Many biomarkers have been proposed for cancer, but only a small fraction of them are clinically useful. This paper describes the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. This is illustrated with the marker TP53, which has been studied in detail but for which there is still no explicit consensus about its clinical value.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146810/1/nyas13947.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146810/2/nyas13947_am.pd

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

European Surgery / Applicability of a shortened interpretation model for intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism in an endemic goiter region

Background In primary hyperparathyroidism (pHPT), quick intraoperative parathyroid hormone monitoring (IOPTH) is performed to predict complete excision of hyperfunctioning tissue and therefore cure. In recent years, efforts have been made to make this prediction more accurate and to shorten the duration of the test, respectively, and therefore reduce waiting and total operating time. The aim of this study was to evaluate the practicability and safety of a time-reduced criterion (decline 35% after 5 min) in a large cohort of patients. Methods In an 11-year period, all patients operated for pHPT were analyzed. After preoperative localization studies, hyperfunctioning parathyroid tissue was removed and IOPTH monitoring was performed. Intraoperatively, a decline of 50% from baseline 10 min after excision of the gland predicted cure. The performance of an interpretation model, using an earlier PTH level was analyzed retrospectively (decline 35% from baseline 5 min after excision). Differences in sensitivity, specificity, positive/negative predictive value and accuracy were calculated. Results According to the inclusion criteria, 1018 patients were analyzed. IOPTH predicted cure in 854 patients (83.9%) 10 min after gland excision with a false positive decline in 13 patients (1.5%). Applying the modified criterion (35% decline within 5 min), 814 patients (80%) showed an appropriate decline (false positive in 18 [2.2%]). Overall, multiple gland disease would have been missed in 7 patients. McNemars test showed a significantly lower sensitivity, specificity and accuracy applying the “35%” criterion. Conclusions In an endemic goiter region, a criterion, demanding a 35% decline 5 min after excision can not be recommended for IOPTH monitoring in patients with pHPT.(VLID)359475

How radical is total parathyroidectomy in patients with renal hyperparathyroidism?

Purpose Total parathyroidectomy (tPTX) in patients with renal hyperparathyroidism (RHPT) aims at the complete removal of all hyperfunctioning parathyroid tissue. Whenever parathyroidectomy is termed “total,” undetectable postoperative parathyroid hormone (PTH) levels within the first postoperative week are expected. The aim of this study was to evaluate if tPTX is technically possible using a radical surgical procedure. Methods In 109 consecutive patients with RHPT (on hemodialysis: n = 50; after kidney grafting n = 59), removal of all visible parathyroid tissue, bilateral thymectomy, bilateral central neck dissection (level VI), and immediate autotransplantation (AT) was performed. Intact PTH (iPTH) levels were measured in the first postoperative week. PTX was classified “total” when iPTH dropped below 10 pg/ml, “subtotal” between 10 and 65 pg/ml, and “insufficient” where levels stayed above 65 pg/ml. Results According to the postoperative PTH value, tPTX was achieved in 80 of 109 (73.4%) patients (hemodialysis n = 27, normal kidney function: n = 43, restricted: n = 10). PTX was “subtotal” in 25 patients (22.9%), 19 on hemodialysis, 2 had normal, and 4 had restricted kidney graft function. PTX turned out to be insufficient in four patients (3.7%); all of them were on hemodialysis. Insufficient PTX was not observed in kidney-grafted patients. Postoperative temporary laryngeal nerve morbidity was 1.8% (no permanent paresis). Conclusions Although applying a very radical concept in patients with RHPT, PTX was “total” in only 73.4%. Persistence of disease was avoided in 91.7%, and low morbidity was documented. In conclusion, it seems difficult to remove all parathyroid tissue from the neck which has to be considered when choosing the surgical procedure.(VLID)363267

Medullary Thyroid Carcinoma : Do Ultrasonography and F-DOPA-PET-CT Influence the Initial Surgical Strategy?

Background At the time of diagnosis, one-third of medullary thyroid carcinoma (MTC) patients show lymph node (LN) or distant metastasis. A metastasized MTC requires different surgical strategies. Objective This study aimed to determine the value of ultrasound and [18F]fluoro-dihydroxyphenylalanine positron emission tomography with computed tomography (F-DOPA-PET-CT) in localizing MTC, as well as LN and distant metastasis. Methods The study included 50 patients (24 males/26 females) with preoperative ultrasound, F-DOPA-PET-CT, and histologically proven MTC. Imaging results were correlated with both preoperative basal calcitonin (bCt) levels and final histology. Results Tumors were classified as pT1a:17 (diameter, mean standard deviation: 5.8 3.0 mm), pT1b:15 (15.0 3.2 mm), pT2:9 (27.3 7.0 mm), and pT3:9 (38.3 24.2 mm). The median bCt level was 202 pg/mL (lower/upper quartile: 82/1074 pg/mL). Ultrasound was positive for tumor in 45/50 (92%) patients (20.0 16.0 mm) and negative in 5 patients (3.2 2.2 mm). Overall, 43/50 (86%) patients had positive F-DOPA local scans (20.0 16.4 mm), while 7 (14%) patients were negative (7.7 8.1 mm). Lastly, 21/50 (42%) patients had LN metastasis; 8/21 (38%) patients had positive LNs suspected with ultrasound, and 12/21 (57%) patients had positive LNs suspected with F-DOPA. Tumor and LN sensitivity of ultrasound was 92% and 43%, respectively, and 86% and 57% of F-DOPA-PET-CT, respectively. In 3/50 (6%) patients and 3/50 (6%) patients, mediastinal LN metastasis and distant metastasis, respectively, were diagnosed only by F-DOPA-PET-CT. Conclusion Ultrasound and F-DOPA-PET-CT are sensitive for the localization of MTC but not for the presence and location of LN metastasis (limitations: size/number). Only F-DOPA ensures the diagnosis of distant metastasis and influences the extent of LN surgery. Surgical strategy cannot be predicted based on neither ultrasound nor F-DOPA-PET-CT. In medullary thyroid carcinoma (MTC), the number of positive lymph nodes (LNs) and involved anatomical compartments are cancer-specific prognostic factors.1 Exact preoperative staging may help to select a stage-adapted surgical strategy. Neck ultrasound is the first imaging modality used in MTC to assess the local extent and regional lymphatic spread. MTC as a neuroendocrine tumor is able to absorb, store, and decarboxylate dopamine. Therefore [18F]fluoro-dihydroxyphenylalanine positron emission tomography with computed tomography (F-DOPA-PET-CT), combining anatomic and ‘functional imaging, may further improve initial local and distal staging of biochemically suspected MTC. F-DOPA-PET-CT is one of the recommended imaging modalities in patients with persistent MTC and basal calcitonin (bCt) levels 150 pg/mL before reoperations;2, 3, 4, 5 however, no studies with a larger patient population evaluating ultrasound in addition to F-DOPA-PET-CT in locating the primary tumor, LN and distant metastasis, and possible consequences to the surgical strategy, have been performed. This prospective observation study aims to determine the value of ultrasound and F-DOPA-PET-CT in radiomorphological detection of primary tumors, identification of possible LN metastasis, and detection of possible distant metastasis before initial surgery, and how a combination of these techniques may help to improve the standardized diagnostic and therapeutic protocol correlating preoperative biochemical and postoperative morphological results.(VLID)360166

Total thyroidectomy (Tx) versus thionamides (antithyroid drugs) in patients with moderate-to-severe Graves ophthalmopathy a 1-year follow-up : study protocol for a randomized controlled trial

Background Graves disease (GD) is characterized by thyrotoxicosis and goiter and arises through circulating autoantibodies that bind to, and stimulate, the thyroid hormone receptor (TSHR). A temporal relation between the onset of hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal manifestation, has been demonstrated. Graves ophthalmopathy (GO) is typically characterized by an inflammation and expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered for hyperthyroidism caused by Graves disease: antithyroid drugs (ATD) (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there is no clear recommendation on the treatment of Graves disease and GO, mainly due to the individuality of the disease in each patient. The aim of the study is to examine the difference in the outcome of GO in patients with moderate-to-severe GO who receive Tx versus further ATD after suffering their first relapse of GO, or in which GO stays the same following the initial decrease in ATD therapy after 6 months. Methods/Design This prospective randomized clinical trial with observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal index measurements via ultrasound, and quality of life score. Discussion This study should allow for better therapeutic choices in patients with moderate-to-severe GO. In addition, it should demonstrate whether the outcome of GO in patients with moderate-to-severe GO is better in those who receive early Tx versus further ATD. Furthermore, this study will aim to establish a standard glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO. Trial registration Eudra-CT: 2015003515-38; Medical University of Vienna Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017. Registered on 27 January 2017.(VLID)468223