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BACKGROUND AND PURPOSE: Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. Recently, it has been suggested that PTH can also enhance bone repair after fracture and distraction osteogenesis. We analyzed bone density and strength of the newly regenerated mineralized tissue after intermittent treatment with PTH in rabbits, which undergo Haversian bone remodeling similar to that in humans. METHODS: 72 New Zealand White rabbits underwent tibial mid-diaphyseal osteotomy and the callus was distracted 1 mm/day for 10 days. The rabbits were divided into 3 groups, which received injections of PTH 25 µg/kg/day for 30 days, saline for 10 days and PTH 25 µg/kg/day for 20 days, or saline for 30 days. At the end of the study, the rabbits were killed and the bone density was evaluated with DEXA. The mechanical bone strength was determined by use of a 3-point bending test. RESULTS: In the 2 PTH-treated groups the regenerate callus ultimate load was 33% and 30% higher, absorbed energy was 100% and 65% higher, BMC was 61% and 60% higher, and callus tissue volume was 179% and 197% higher than for the control group. INTERPRETATION: We found that treatment with PTH during distraction osteogenesis resulted in substantially higher mineralized tissue volume, mineral content, and bending strength. This suggests that treatment with PTH may benefit new bone formation during distraction osteogenesis and could form a basis for clinical application of this therapy in humans. [ABSTRACT FROM AUTHOR]

Background: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with 18 F-FDG PET/CT (FDG PET/CT), combined 111 In-WBC/ 99m Tc-Nanocoll, and 99m Tc-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm., Materials and Methods: Fifty-five patients underwent imaging with 99m Tc-HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up., Results: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74-1.00), a specificity of 97% (CI 0.82-1.00), and an accuracy of 98% (CI 0.88-1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74-1.00), 71% (CI 0.56-0.90), and 79% (CI 0.68-0.93), respectively., Conclusions: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.

Objective: Hepatobiliary scintigraphy (HBS) is an important tool in diagnosing biliary atresia in infants. There is limited evidence on the use of single photon emission computed tomography/computed tomography (SPECT/CT) as an additional imaging method to planar imaging. We evaluated the value of SPECT/CT in unclear cases of planar HBS., Subjects and Methods: Consecutive patients with suspected biliary atresia who underwent guideline-compliant HBS from January 2010 until March 2020 were reviewed, and cases with SPECT/CT were identified. Each step within the imaging procedure (dynamic, static [early and late], and SPECT/CT) was blindly reread in consensus by two observers and categorized based on a 5-point scale: 0, definitely no bowel excretion (i.e., atresia confirmed); 1, probably positive; 2,equivocal; 3, probably negative; and 4, definite negative (i.e., atresia not confirmed). In this analysis, categories were dichotomized as negative for biliary atresia (scores 3-4) or positive (scores 0-2, including equivocal scans). Available follow-up information constituted the standard of truth (SoT)., Results: Twenty-three infants had HBS, among which ten (4 boys and 6 girls; mean age 36 days; range 8-108) underwent SPECT/CT. Single photon emission computed tomography SPECT/CT was performed as early examination (<8h) in 3 subjects and late (8 to 24 h) in 7 infants. Reread SPECT/CT was categorized as positive for atresia in three infants and negative in seven infants. The SoT showed biliary atresia in one of ten patients. Single photon emission computed tomography/CT was true positive in one case, false positive in two, and true negative in seven. No false negative cases were noted. The diagnostic performance of SPECT/CT showed a sensitivity of 100%, specificity of 78%, positive predictive value (PPV) of 33%, negative predictive value (NPV) of 100%, and accuracy of 90%. For comparison, the diagnostic performance of planar HBS showed a sensitivity of 100%, specificity of 67%, PPV of 25%, NPV of 100%, and accuracy of 70%. In summary, the addition of SPECT/CT to planar HBS improved specificity andaccuracyand marginally improved PPV. Single photon emission computed tomography/CT provided more confidence in the final conclusion in 8/10 patients. In the remaining two cases, SPECT/CT did not improve the level of confidence (one remained equivocal, and one changed from probably no excretion to equivocal)., Conclusion: These preliminary data demonstrated increased accuracy of add-on SPECT to planar HBS predominantly due to improved specificity. This finding is consistent with the existing but limited literature and supports the recommendation of routine use of SPECT/CT or SPECT.

Objective: The correlation between the computer-assisted bone scan index (BSI) responses versus clinical response classification if bone metastases in prostate cancer patients are not clear. We compared changes in BSI with Prostate Cancer Working Group-3 (PCWG3) and MD Anderson (MDA) criteria., Materials and Methods: Fifty-six consecutive patients with at least two bone scans (BS) within 12 months were included, who had BS before and after treatment with the same anticancer agent., Results: Progressive disease (PD) by PCWG3 criteria was seen in 28% of the cases (median BSI increased by 1.69 units) versus non-PD in 72% (BSI change -0.13). MDAnderson showed PD in 34% (BSI increase 0.49), 45% stable disease (BSI change 0.00), and 20% partial responses (BSI decrease 1.44). Absolute BSI changes differed significantly among response categories by PCWG3 and MDA criteria (both P<0.0001). Response classification using dichotomized BSI data (>0/≤0 and >0.3/≤0.3 BSI units) showed a significant correlation with PCWG3 and MDA criteria (all P<0.001). Absolute BSI changes and dichotomized BSI correlated to prostate-specific antigen responses (both P<0.001) but not to clinical responses., Conclusion: Absolute changes in BSI and BSI response classification correlated significantly with standardized clinical response criteria for the assessment of treatment responses of skeletal metastases in prostate cancer.

Objective: To investigate inter- and intraobserver agreement using standard (std)-single-photon emission computed tomography/computed tomography (SPECT/CT) or ultra-fast acquisition (UF)-SPECT/CT as an add-on to planar whole-body bone scintigraphy (WB-BS) for the detection of bone metastases in patients with known cancer., Methods: Images from patients (n = 104) participating in a prospective trial comparing SPECT/CT as an add-on to WB-BS with two different acquisition methods (std-SPECT/CT; 20 s per view, 32 views and UF-SPECT/CT; 16 views of 10 s per view) were included. The combinations of WB-BS with the two different SPECT/CT acquisition methods were independently evaluated by two experienced observers using a three-point scale (M0: no metastases, Me: equivocal for bone metastases and M1: bone metastases). The observers re-evaluated the scans 6 months later. Inter- and intraobserver agreement was calculated using linear weighted kappa., Results: The linear weighted kappa for the interobserver agreement was 0.78 [95% confidence interval (CI) 0.61-0.94] for WB-BS with std-SPECT/CT and 0.84 (95% CI 0.67-1.00) for WB-BS with UF-SPECT/CT. Similar values were observed for the intraobserver agreement, in which the linear weighted kappa was 0.76 (95% CI 0.60-0.92) and 0.73 (95% CI 0.57-0.90) for std-SPECT/CT and UF-SPECT/CT, respectively., Conclusion: Satisfactory inter- and intraobserver agreement was seen for both acquisition methods, emphasizing that the use of SPECT/CT as an add-on to WB-BS is a robust method for the detection of bone metastases even when conducted with a very short acquisition time.

The predominant indications for revision surgery after total hip (THA) or knee arthroplasty (TKA) are an aseptic failure (AF) and prosthetic joint infection (PJI). Accurate diagnosis is crucial. Therefore, we evaluated prospectively a multidisciplinary diagnostic algorithm including multi-modal radionucleid imaging (RNI) and extended microbiological diagnostics. If the surgeon suspected PJI or AF, revision surgery was performed with multiple samples obtained in parallel for special culture procedures and later molecular analyses. Alternatively, if the underlying cause was not evident, RNI was scheduled comprising 99 Tc - HDP SPECT/CT, 111 In-labeled white blood cells combined with 99 Tc-nanocoll bone marrow SPECT/CT, and 18 F-FDG PET/CT. A multidisciplinary clinical team made a recommendation on the indication for a diagnostic procedure guided by RNI images or revision surgery. A total of 156 patients with 163 arthroplasties were included. Fifty-five patients underwent RNI. In all, 118 revision surgeries were performed in 112 patients: 71 on the indication of AF and 41 revision of PJI. Thirty-four patients were concluded with chronic pain, and revision surgery refrained. The effective median follow-up period was 13 months. A structured approach offered by the algorithm was useful for the clinician in the evaluation of patients with a failing TKA or THA. Surgical revision was possibly obviated in approximately 20% of patients where an explanation or cause of failure was not found. The algorithm served as an effective tool., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Unrecognized periprosthetic joint infections are a concern in revision surgery for aseptic failure (AF) after total hip (THA) or knee (TKA) arthroplasties. A gold diagnostic standard does not exist. The aim of the current study was to determine the prevalence of unrecognized periprosthetic joint infection (PJI) in a cohort of revision for AF, using an experimental diagnostic algorithm., Methods: The surgeons' suspicion of AF was based primarily on patient history and clinical evaluation. X-ray imaging was used to reveal mechanical problems. To rule out an infectious aetiology standard blood biochemical tests were ordered in most patients. Evaluation followed the existing practice in the institute. Cases were included if revision surgery was planned for suspected AF. Intraoperatively, five synovial tissue biopsies were obtained routinely. PJI was defined as ≥3 positive cultures with the same microorganism(s). Patients were followed for 1 year postoperatively. Protocol samples included joint fluid, additional synovial tissue biopsies, bone biopsy, swabs from the implant surface, and sonication of retrieved components. Routine and protocol samples were cultured with extended incubation (14 days) and preserved for batchwise 16S rRNA gene amplification. Patients were stratified based on culture results and a clinical status was obtained at study end., Results: A total of 72 revisions were performed on 71 patients (35 THA and 37 TKA). We found five of 72 cases of unrecognized PJI. Extended culture and protocol samples accounted for two of these. One patient diagnosed with AF was treated for a PJI during follow-up. The remaining patients did not change status from AF during follow-up., Conclusions: We found a low prevalence of unrecognized periprosthetic joint infections in patients with an AF diagnosis. The algorithm strengthens the surgeons' preoperative diagnosis of a non-infective condition. Evaluation for a failing TKA or THA is complex. Distinguishing between AF and PJI pre-operatively was a clinical decision. Our data did not support additional testing in routine revision surgery for AF.

Objective: The aim of this study was to investigate the contribution of contrast-enhanced computed tomography (CE-CT) to the localization of parathyroid adenomas compared with the dual-phase Tc-99m MIBI SPECT with low-dose CT (LD-CT)., Patients and Methods: This retrospective study included consecutive patients with primary hyperparathyroidism who underwent a preoperative dual-phase MIBI SPECT/CT followed by surgical resection. The standard of care was dual-phase MIBI SPECT/CT, acquired with LD-CT in the early phase and CE-CT in the late phase (SPECT/CE-CT). The presence and localization of positive sites were extracted from study reports. To examine the role of CE-CT, patient cases were independently re-reviewed, with the early LD-CT fused with early and late SPECT (SPECT/LD-CT). The two SPECT/CT methods were compared for sensitivity, and the positive predictive value and histopathology were used as a reference., Results: In total, 138 patients were included. The investigation was positive for suspected adenomas in 124 patients using SPECT/CE-CT and in 122 patients using SPECT/LD-CT. The per-patient sensitivity was 87.5% [95% confidence interval (CI): 80.7-92.6%] for SPECT/CE-CT and was not statistically significantly different from SPECT/LD-CT (85.3%; 95% CI: 78.2-90.8%) (P=0.39). The positive predictive value was 95.2% (95% CI: 95.4-99.9%) with SPECT/CE-CT versus 100% (95% CI: 96.8-100%) with SPECT/LD-CT. For small adenomas (≤500 mg), the sensitivity was low with SPECT/CE-CT (67%) as well as with SPECT/LD-CT (64%)., Conclusion: Late CE-CT, compared with late LD-CT, did not significantly improve the sensitivity of dual-phase Tc-99m MIBI parathyroid SPECT/CT in a population of patients with primary hyperparathyroidism. These findings were consistent regardless of the size, location, or histology of the adenomas.

Background: The aim of this study is to assess whether ultra-fast acquisition SPECT/CT (UF-SPECT/CT) can replace standard SPECT/CT (std-SPECT/CT) as "add-on" to whole-body bone scintigraphy (WB-BS) for the investigation of bone metastases. Consecutive cancer patients referred for WB-BS who underwent SPECT/CT in addition to WB-BS were included. Std-SPECT, UF-SPECT, and low-dose CT were performed (std-SPECT: matrix 128 × 128, zoom factor 1, 20 s/view, 32 views; UF-SPECT: identical parameters except for 10 s/view and 16 views, reducing the acquisition time from 11 to 3 min). A consensus diagnosis was reached by two observers for each set of images (WB-BS + standard SPECT/CT or WB-BS + UF-SPECT/CT) using a three-category evaluation scale: M0: no bone metastases; M1: bone metastases; and Me: equivocal findings., Results: Among the 104 included patients, most presented with prostate cancer (n = 71) or breast cancer (n = 28). Using WB-BS + std-SPECT/CT, 71 (68%) patients were classified as M0, 19 (18%) as M1, and 14 (14%) as Me. Excellent agreement was observed between WB-BS + std-SPECT/CT and WB-BS + UF-SPECT/CT using the three-category scale: kappa = 0.91 (95% CI 0.84-0.97). No difference in observer agreement between cancer types was detected. SPECT/CT provided a definitive classification in 90 of 104 cases in which WB-BS was not entirely diagnostic., Conclusions: To investigate potential bone metastases, UF-SPECT/CT can be conducted as add-on to WB-BS to notably reduce the SPECT acquisition time without compromising diagnostic confidence.

Purpose: The aim of this study was to assess observer agreement on the evaluation of treatment responses of bone metastases by bone scintigraphy (BS) using different scoring methods in prostate cancer patients., Patients and Methods: Sixty-three paired BS from 55 patients were included. BS was performed before and after more than 12 weeks of anticancer treatment. A panel of experienced nuclear medicine physicians from several institutions evaluated treatment response using three different methods: (a) standard clinical assessment, (b) MD Anderson criteria, and (c) Prostate Cancer Working Group 2 (PCWG-2) criteria. All methods were based on the evaluation of paired before-after bone scans., Results: Readers were able to classify the presence of bone metastases at baseline with a high level of agreement [Cohen's κ=0.94, 95% confidence interval (CI) 0.82-1.00]. Observer agreement on bone response by PCWG-2 criteria showed considerable agreement (Cohen's κ=0.84, 95% CI: 0.69-0.99). Evaluation using standard clinical assessment and MD Anderson criteria showed moderate agreement (0.52, 95% CI: 0.36-0.69 and 0.64, 95% CI: 0.48-0.79, respectively). There was considerable variation among readers for regional lesion count on individual scans, with limits of agreement of -10 to 10 lesions or more for the majority of anatomical regions, including the thorax, spine, and pelvis., Conclusion: Observer agreement on treatment response by BS varied notably across methods. Optimal agreement was achieved by the PCWG-2 criteria. Variation in the classification of treatment response of bone metastases may have a significant impact on clinical decision-making, emphasizing the need for a uniform approach, including during clinical practice. Response assessment by lesion counting on repeated BS without access to previous scans cannot be recommended.

Purpose of the Report: When thyroid scintigraphy (TS) is performed after contrast-enhanced CT (CE-CT), tracer uptake of 99mTcO4 in the thyroid gland can be inhibited by free iodide. Currently, it is recommended to postpone TS until 4 to 8 weeks after CE-CT, but few data exist to support this recommendation. The purpose was to investigate the effect of CE-CT and other variables for the diagnostic quality of TS., Patients and Methods: This retrospective study included 196 patients subjected to TS less than 3 months after a CE-CT (median, 66 days). Patients with elevated thyroid-stimulating hormone (>4.5 mIU/L) or suspected thyroiditis were excluded. Logistic regression was used to calculate the probability of a TS of diagnostic quality with the variables days since CE-CT, age, thyroid-stimulating hormone, and kidney function (eGFR)., Results: Days since CT and age were highly significant (P < 0.001) predictors for diagnostic TS. The probability of diagnostic quality TS after CE-CT increased with time and reached approximately 70% to 80% 6 to 8 weeks after CE-CT. Analysis of age-specific populations showed age to be a strong independent factor., Conclusions: Our findings are in consensus with the currently recommended interval of 6 to 8 weeks between CE-CT and TS. However, our results indicate that patient age should be taken into account, and we suggest the following delay from CE-CT to TS: 4 weeks for patients aged younger than 50 years, 6 weeks for patients aged 50 to 60 years, and 8 weeks for patients aged older than 60 years.

Background and Purpose: A proximal stem centralizer may be beneficial regarding cementing pressures, cement penetration, and stem alignment. We measured these parameters when cementing a mat-surfaced femoral component with and without the use of a proximal stem centralizer., Material and Methods: 8 femoral prostheses with proximal centralizers and 8 femoral prostheses without proximal centralizers were cemented according to third-generation cementing technique in 8 pairs of embalmed cadaveric femora. We recorded intramedullary pressures (peak levels, the area under the pressure curves and mean pressure) with 6 pressure transducers during stem cementation. Computer tomographic scanning of specimens was performed to evaluate stem alignment after surgery. Thickness of the cement mantle, cement penetration, and stem centralization at the metaphyseal part of the femur were measured on cross sections using stereology., Results: There were no statistically significant differences in measured pressure and cement penetration values between the groups. There was similar cement distribution around the stems; however, in using a proximal centralizer, the cement mantle tended to be thinner laterally. Moreover, we found a larger variation in stem alignment on lateral projection in the proximal centralizer group., Interpretation: No benefits regarding intramedullary pressures and cement penetration were obtained from cementation of a straight stem with a proximal stem centralizer. However, there was an increased risk of inferior stem positioning in the reamed medullary cavity using the centralizing device.

Unlabelled: Since the approval of parathyroid hormone (PTH) as treatment for osteoporosis, PTH has increasingly been investigated for bone repair and regeneration. The aim of the study was to investigate the effects of intermittent PTH treatment on the microstructure of regenerated mineralizing tissue after distraction osteogenesis in rabbits. After tibial mid-diaphyseal osteotomy the callus was distracted 1 mm/day for 10 days. 72 rabbits were divided in to 3 groups, which daily received a PTH (1-34) 25 microg/kg injection for 30 days; a saline injection for 10 days and a PTH injection for 20 days; or a saline injection for 30 days. The microstructure of the regenerate was assessed by micro computed tomography (microCT). In all 51 obtained specimens were evaluated morphometrically using three different volumes of interests. The results showed that treatment with PTH during distraction osteogenesis resulted in a significantly higher trabecular number, a more isotropic trabecular orientation, a higher connectivity density, and a higher mineralizing tissue mass. We also found that distraction calluses treated with PTH were more mature than the non-treated., Conclusion: treatment with PTH resulted in an enhanced microstructure of the newly regenerated mineralizing tissue indicating that PTH has a potential role as a stimulating agent during distraction osteogenesis.

Objective: The overall purpose of the study is to determine the effects of parathyroid hormone (PTH) (1-34) on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening in rabbits. Additionally the aim of the pilot study is to titrate the optimal dose of PTH for distraction osteogenesis treatment in rabbits' tibial lengthening model., Materials and Methods: A total of 18 rabbits underwent right tibia lengthening by callus distraction. Lengthening was started 5 days postoperatively 1 mm/day for a 10-day period and consolidation of 20 days followed. Rabbits were divided into three groups: group I received PTH (1-34) treatment at a dose of 5 microg/kg/day, group II received treatment with PTH (1-34) at a dose of 25 microg/kg/day; group III rabbits were treated with saline. After euthanasia, tibiae of both legs were dissected free, kept frozen and underwent x-ray analysis, dual x-ray absorptiometry-scanning, microcomputed tomography scanning and three-dimensional evaluation and mechanical test followed., Results: Over all, during distraction osteogenesis in a new regenerated bone, PTH (1-34) treatment with two different doses of 5 microg/kg/day and 25 microg/kg/day increased callus cross-sectional area, callus bone mineral density and bone mineral content, bone volume density; dramatically increased trabecular number with slight increase in trabecular thickness, whereas decreased trabecular separation, bone surface density and decreased degree of anisotropy when compared to control group animals., Conclusion: PTH (1-34) treatment improved mineralization, structural indices of regenerated distracted rabbits' tibiae, whereas treatment at a dose of 25 microg/kg/day PTH (1-34) was significantly more effective than 5 microg/kg/day PTH(1-34) dose treatment when compared to control group. Bigger dose has been chosen for the main study.

Parathyroid hormone naturally secreted by the parathyroid glands is a potent anabolic agent for bone. Parathyroid hormone is primarily thought of as a catabolic protein involved in the physiologic release of calcium from bone. Whereas during recent years, a number of animal studies and clinical trials have demonstrated that intermittent parathyroid hormone administration induces anabolic effects on both cancellous and cortical bone, enhances bone mass and increases mechanical strength of the bones. Most of the studies, both animal and human, have addressed the treatment of osteoporosis and parathyroid hormone represents an important new advance in the therapy of osteoporosis. Few studies have investigated the effect of intermittent parathyroid hormone treatment in the field of orthopedics on fracture healing and fixation of orthopedic implants. The results of those studies indicated an enhancement of fracture healing, faster bone repair and better fixation of the implant. Recently there were few animal studies started to investigate the effects of parathyroid hormone treatment on bone formation in regenerated and surrounding bone of distracted callus during limb lengthening. Distraction osteogenesis is a technique for bone lengthening that is widely used clinically and experimentally. Newly forming bone during distraction osteogenesis is expected to be an appropriate pattern for parathyroid hormone anabolic effect. Preclinical studies as well as clinical trials suggest that parathyroid hormone might be useful as a stimulator of bone formation whereas a lot of questions regarding parathyroid hormone therapy remain unanswered and require further experimental studies and investigations.