Skeletal Lesions Research Articles

CLINICAL FEATURES OF CONNECTIVE TISSUE DYSPLASIA, OSGOOD-SCHLATTER DISEASE AND MULTIPLE CORTICAL DISORDERS IN A CHILD.

The aim: To analyze scientific data on the problems of disorders of bone morphogenesis in children, in particular, non-ossifying fibroma. To analyze modern methods of diagnosis and treatment of this disease in the context of the latest scientific achievements. Materials and methods: The latest data of scientists from the world's leading clinics describing various forms of fibrous skeletal lesions in children of differ¬ent ages were analyzed. We examined a boy with fibrous lesions of the cortical layer of the knee joint bones and a girl with a large fibrous focus of the distal femoral metaphysis, which resulted in a closed pathological bone fracture. Surgical treatment, osteosynthesis, marginal resection of the tumor, bone grafting and histological examination were conducted. Conclusions: Despite numerous studies of this disease, the etiopathogenesis of this disease has not been studied. There are no early symptoms of fibrous bone lesions in children. Diagnosis is possible only when a pathological fracture of the affected bone occurs due to extensive growth of fibrous tissue and a significant decrease in the mechanical strength of the bone. Most cases of recognition of such a disease occur accidentally when performing X-ray examinations for other reasons - bruises, sprains, arthralgias, osteochondropathy, infectious diseases, etc. It is known that boys are more mobile and require more frequent X-ray examinations for limb injuries than girls, so the likelihood of accidental detection of such changes increases significantly. Thus, long-term observations of children with fibrous bone lesions have shown that after 40 years, patients rarely developed malignant tumors - osteogenic sarcoma, fibrosarcoma, malignant fibroma of tubular bones, pelvic bones. There are no early symptoms of fibrous bone lesions in children. Recognition of such a disease occurs by chance when X-ray examinations are performed for other reasons.

Study on the Effect of Low Calcium Dialysate on Biochemical Profile of Adynamic Bone Disease in Patients on Maintenance Hemodialysis.

In recent years, adynamic bone disease (ABD) has become a common skeletal lesion in adult patients with chronic kidney disease. We aimed to compare the effects of low calcium dialysate (LCD) and standard calcium dialysate of our facility [high calcium dialysate (HCD)] on the evolution of bone and mineral parameter related to ABD in dialysis patients. Forty patients with predialysis intact parathyroid hormone (iPTH) <100 pg/mL and/or bone-specific alkaline phosphatase (BAP) <27 U/L were included in this study and were equally distributed over LCD (1.25 mmol/L) or HCD (1.75 mmol/L) treatment. The duration of the study was 6 months. There was no significant difference in baseline characters and biochemical parameters related to chronic kidney disease-mineral and bone disorder in both the groups. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly lower in the LCD group versus HCD at the end of the study. The mean serum levels of iPTH, total alkaline phosphatase, and BAP in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels. The bone markers in the HCD group did not change significantly. At the end of the study, all bone parameters in the LCD group were significantly higher than in the HCD group. Development of measures indicating increased bone turnover in patients receiving 1.25 mmol/L of dialysate calcium, most likely as a result of inhibiting a positive calcium balance and allowing for long-term PTH secretion stimulation. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

Usefulness of virtual autopsy in diagnosing pathologies in the paediatric population: A systematic review.

Virtual autopsy is a non-invasive/minimally invasive method for conducting an autopsy, with the assistance of imaging techniques. We aim to review the benefits of virtual autopsy in detecting pathologies in the paediatric population. The procedure adhered to Institute of Medicine and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Seven databases including MEDLINE and SCOPUS were searched for articles published 2010-2020 worldwide in English. A narrative synthesis of the findings of included studies was carried out to discuss and summarize the results of the review. From 686 studies on paediatric deaths, 23 met selection/quality criteria. Virtual autopsy was better than conventional autopsy in detecting skeletal lesions and bullet trajectory, thus a crucial tool in the investigation of traumatic and firearm deaths. Virtual autopsy was superior to conventional autopsy in identifying the point of bleeding in postoperative deaths and objectively quantifying air/fluid in body cavities. Virtual autopsy was a useful adjunct for detecting pulmonary thrombo-embolism, foreign body aspiration, drowning and metastatic malignancies. The use of non-contrast imaging in investigating natural paediatric deaths did not offer more information than conventional autopsy. Misinterpretation of normal post-mortem changes as pathological findings was another disadvantage of virtual autopsy leading to erroneous conclusions. But accuracy may be improved with contrast enhancement and post-mortem magnetic resonance imaging. Virtual autopsy is a crucial tool in the investigation of traumatic and firearm deaths in the paediatric population. Virtual autopsy will be useful as an adjunct to conventional autopsy in asphyxial deaths, stillbirths and decomposed bodies. Virtual autopsy has limited value in differentiating antemortem and post-mortem changes with the added risk of misinterpretations, therefore should be used with caution in natural deaths.

Tuberculosis of the Elbow Joint – A Rare Case Report

Musculoskeletal tuberculosis accounts for nearly 10% of all extra pulmonary cases with spine being the most common site. Tuberculosis involving the elbow joint is extremely rare accounting for less than 5% of all skeletal lesions. Early diagnosis and treatment is crucial to prevent serious joint and bone destruction. Here, we present a rare case of primary TB elbow joint in a 46 year old female.

Co-Targeting Luminal B Breast Cancer with S-Adenosylmethionine and Immune Checkpoint Inhibitor Reduces Primary Tumor Growth and Progression, and Metastasis to Lungs and Bone.

Breast cancer (BCa) is the most prevalent cancer in females and has a high rate of mortality, especially due to increased metastasis to skeletal and non-skeletal sites. Despite the marked clinical accomplishment of immune checkpoint inhibitor (CPI) therapy in patients with several cancers, it has had limited success in luminal subtypes of BCa. Accordingly, recent efforts have focused on combination therapy with CPI, including epigenetic modulators, to increase response rates of CPI in luminal BCa. We have previously shown that S-adenosylmethionine (SAM), the ubiquitous methyl donor, has strong anti-cancer effects in various cancers, including all subtypes of BCa. In the current study, we took a novel approach and examined the effect of CPI alone and in combination with SAM on tumor growth and metastasis in a syngeneic mouse model of luminal B BCa. We showed that SAM decreases cell proliferation, colony-formation (survival), and invasion of luminal B BCa cell lines (Eo771, R221A) in vitro. In in vivo studies, in Eo771 tumor-bearing mice, either SAM or anti-PD-1 antibody treatment alone significantly reduced tumor growth and progression, while the SAM+anti-PD-1 combination treatment had the highest anti-cancer efficacy of all groups. The SAM+anti-PD-1 combination reduced the percentage of animals with lung metastasis, as well as total metastatic lesion area, compared to control. Additionally, the SAM+anti-PD-1 combination significantly reduced the skeletal lesion area and protected tibial integrity to a greater extent than the monotherapies in an Eo771 bone metastasis model. Transcriptome analysis of Eo771 primary tumors revealed significant downregulation of pro-metastatic genes, including Matrix metalloproteinases (MMPs) and related pathways. On the other hand, CD8+ T cell infiltration, CD8+ T cell cytotoxicity (elevated granzymes), and immunostimulatory genes and pathways were significantly upregulated by the combination treatment. The results presented point to a combination of SAM with CPI as a possible treatment for luminal B BCa that should be tested in clinical studies.

Physeal fusion status and lesion size are more important than patient age for healing of juvenile osteochodritis dessicans lesions of the distal femur.

The purpose of the study was to evaluate the effect of skeletal age and lesion size, location, and grade on the success of nonoperative treatment for juvenile osteochondritis dissecans (OCD). It is hypothesized that skeletal maturity, including a combination of maturation phenotypes, correlates with nonoperative lesion healing. The clinical and radiographic data on 52 patients aged 7-20years treated for OCD of the distal femur between 2010 and 2019 were retrospectively reviewed. Knee radiographs were assessed for number of lesions present and lesion location, size, and stage. Assessments of skeletal maturation were performed on all antero-posterior knee radiographs using the Roche, Wainer, and Thissen (RWT) method. Patients were categorized as healed if they demonstrated no pain on clinical examination. The relationship between skeletal maturity and nonoperative lesion healing was determined using Spearman rank correlations on available variables. Neither chronological nor skeletal age was associated with surgical status (Rho = 0.03, n.s., and Rho = 0.13, n.s., respectively) or the healing status of nonoperatively treated OCD lesions (Rho = 0.44, n.s., and Rho = 0.03, n.s., respectively). Epiphyseal fusion status of the distal femoral physis was moderately correlated with nonoperative healing, but was not statistically significant (lateral femoral physis: Rho = 0.43, p = 0.05; medial femoral physis: Rho = 0.43, n.s.). Lesion length correlated with surgical status (Rho = -0.38, p = 0.009). The extent of fusion of the distal femoral physis (multi-stage grading) may be more strongly correlated with nonoperative healing than other markers of skeletal maturity or chronological age. Clinicians can use this as an additional radiographic sign when considering nonoperative treatment for juvenile OCD lesions in the distal femur. OCD lesion length and physeal fusion status appear to be more important for healing than patient age.

Clinical characteristics of 18 children with chronic nonbacterial osteomyelitis

Objective: To investigate the clinical features of children with chronic nonbacterial osteomyelitis (CNO), and raise awareness among clinicians. Methods: In this retrospective study, 18 patients with CNO who were diagnosed in Children's Hospital of Fudan University from January 2015 to December 2021 were included. Results: Eighteen children with CNO (12 males, 6 females) were identified. Their age at onset was 9 (5, 11) years, the delay in diagnosis was 2 (1, 6) months, and follow-up-was 17 (8, 34) months. The most common symptoms were fever in 14 children, as well as bone pain and (or) arthralgia in 14 children. In terms of laboratory results, normal white blood cell counts were observed at onset in 17 patients; increased erythrocyte sedimentation rate (ESR) in all patients; increased C reactive protein (CRP) over the normal value in 14 patients. Of the 18 patients, 2 had positive antinuclear antibodies, while none had positive human leukocyte antigen-B27 or rheumatoid factor. Imaging examination revealed that all the patients had symmetrical and multifocal skeletal lesions. The number of structural lesions detected by imaging investigation was 8 (6, 11). The most frequently affected bones were tibia in 18 patients and femur in 17 patients. Bone biopsy was conducted in 14 patients and acute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. Magnetic resonance imaging (MRI) found bone lesions in all the patients and bone scintigraphy were positive in 13 patients. All the patients were treated with nonsteroidal anti-inflammatory drugs, among whom 10 cases also treated with oral glucocorticoids, 9 cases with traditional disease modifying anti-rheumatic drugs, 8 cases with bisphosphonates and 6 cases with tumor necrosis factor inhibitors. The pediatric chronic nonbacterial osteomyelitis disease activity score, increased by 70% or more in 13 patients within the initial 6-month follow-up. Conclusions: The clinical manifestations of CNO are lack of specificity. The first symptom of CNO is fever, with or without bone pain and (or) arthralgia, with normal peripheral blood leukocytes, elevated CRP and (or) ESR. Whole body bone scanning combined with MRI can early detect osteomyelitis at subclinical sites, and improve the diagnostic rate of CNO.

The association between skeletal lesions and tuberculosis in a pre-antibiotic South African sample

ObjectiveThis study assessed the sensitivity and specificity of skeletal lesions to accurately diagnose TB in a pre-antibiotic South African skeletal sample. MaterialsA total of 435 skeletons of individuals who died before 1950 from the Raymond A. Dart Collection of Human Skeletons. 176 died of TB, 109 died of other pulmonary diseases, and 150 died of other causes. MethodsThe presence / absence of 23 skeletal lesions were assessed for differences in frequency between groups. Sensitivities and specificities were calculated and compared to Dangvard Pedersen et al. (2019). ResultsLesions on the ventral surface of thoracic and lumbar vertebral bodies were observed significantly more often in TB and pulmonary cases than in other cause of death group and yielded a 55% probability of a true TB diagnosis, if observed. An association between skeletal lesions and TB was found for rib and vertebral lesions. ConclusionsThe results suggest that even when not documented to have died of TB, TB-related changes are observed in many individuals in a South African skeletal sample, indicating that they may have been infected with the disease. SignificanceThe study provides information that can assist palaeopathologists in making inferences about the prevalence of TB in past populations. LimitationsSample sizes were small, and the inclusion of a pulmonary disease group may have confounded the results. Suggestions for further researchThe selection of a control group without any possible contact with TB may improve the results and should be investigated.

Infantile Pompe disease with intrauterine onset: a case report and literature review

BackgroundPompe disease is a rare autosomal recessive disease. Acid alpha−glucosidase (GAA) deficiency leads to glycogen storage in lysosomes, causing skeletal, cardiac, and smooth muscle lesions. Pompe disease is progressive, and its severity depends on the age of onset. Classic infantile Pompe disease, the most severe form, is characterized by an age of onset before 12 months. Pompe disease with intrauterine onset has rarely been reported.Case presentationThe proband was born at a gestational age of 40 weeks and 3 days and admitted to our hospital because of intrauterine cardiac hypertrophy, shortness of breath, and cyanosis until 13 min postnatally. Physical examination at admission revealed poor responsiveness, pale skin, shortness of breath, reduced limb muscle tone, and bilateral pedal edema. The heart sounds were weak, and no heart murmur was heard. Echocardiography showed left (9 mm) and right (5 mm) ventricular hypertrophies. The patient was subjected to non−invasive ventilator−assisted respiration, fluid restriction, diuresis, and metoprolol treatment. Infantile Pompe disease was diagnosed on day 16 with a GAA enzymatic activity of 0.31 µmol/L/h and with the full−penetrance genetic test showing the homozygous gene mutation c.1844G>T(p.Gly615Val). Enzyme replacement therapy was refused by the patient’s parents, and the patient died at seven months of age from cardiopulmonary failure.ConclusionInfants with intrauterine−onset Pompe disease usually have early manifestations of heart disease. Prompt GAA enzymatic activity determination and molecular genetic testing are helpful in aiding the parents’ decision and planning the treatment.

Occult ischemic bone lesions in children with sickle cell disease: A study of prevalence.

Avascular necrosis (AVN) is a severe complication of sickle cell disease (SCD) and involves principally the femoral head. Few data exist about the prevalence of lesions in other segments. In this cross-sectional study, 42 children (20 males and 22 females) underwent a magnetic resonance imaging (MRI) of the spine, upper arms, and femurs. The primary outcome was to define the prevalence and locations of bone infarcts. Forty-two patients completed the study; the total median age was 11.9 years (interquartile range=9.5-13.9). Eleven patients (26.2%) were positive for altered bone findings for a total of 32 lesions. Most of the lesions were in the humerus 17 (53.1%), 11 (34.4%) in the femurs, and 4 (12.5%) in the vertebrae. The median number of vaso-occlusive crises (VOCs) was two and four for patients without and with bone lesions, respectively (p=.01). The annual rate of VOC is the best marker for the positive MRI (odds ratio=82.6; p=.03), and it is correlated with the number of sites involved (p=.02). Our study highlights that the prevalence of skeletal lesions could be underestimated, and it provides the basis for clinical reasoning and tailored therapy in SCD children.

Whole-body magnetic resonance imaging for staging Langerhans cell histiocytosis in children and young adults.

Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative. We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria. Two national study protocols were independently designed, and data were then pooled to increase the power of their findings. R-SS and WB-MRI were performed at diagnosis and repeated at the follow-up to confirm the nature of the identified lesions and to study their evolution. Data from 67 patients were analyzed (52 from Italy and 15 from Austria). Compared to R-SS, WB-MRI identified 29 additional skeletal lesions in 14 patients (including two false-positive lesions). Two skeletal lesions were detected at R-SS and missed at WB-MRI (false negative). Per-lesion sensitivity rates were 78.6% (95% CI: 71.0-85.9) for R-SS and 98.4% (95% CI: 94.4-99.8) for WB-MRI, respectively. Based on WB-MRI findings, six patients would have been upstaged to a higher risk class than staging with R-SS. WB-MRI had a significantly higher detection rate for skeletal lesions compared to R-SS. Clinical and radiology expertise is required to avoid upstaging and overtreatment.

KLF15/mTOR related proteins involved in effect of aerobic interval training on improving skeletal muscle lesions in rats with type 2 diabetes

Objective: To investigate the effects of aerobic intermittent exercise on the expressions of KLF15/mTOR related proteins to improve skeletal muscle lesions in type 2 diabetes rats. Methods: The experimental model of type 2 diabetes rats was established by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin (STZ). After modeling, rats were randomly divided into two groups: diabetes model group (DM), diabetes+exercise group (DE), and normal rats were set as control group (C), 10 rats in each group. Group DE was given 8-week aerobic intermittent treadmill exercise intervention, while group C was not given any intervention. At the end of the experiment, the expressions of KLF15, mTOR, p-mTOR, and cleared caspase-3 in gastrocnemius muscle were detected by Western blot. The histopathologic changes of gastrocnemius were observed under microscope; skeletal muscle cells apoptosis rates and muscle mass were examined respectively using HE staining and TUNEL fluorescence staining. At the same time, changes of blood glucose and serum insulin, and weight were examined in the end of the experiment. Results: ①Compared with group C, the wet weight of gastrocnemius muscle and body weight, ratio of wet gastrocnemius muscle and body weight in group DM were decreased(P＜0.05 or P＜0.01); compared with group DM, the wet weight of gastrocnemius muscle, ratio of wet gastrocnemius muscle and body weight in the group DE were increased significantly (P＜0.05). ②Compared with group C, the fasting blood glucose level of group DM was increased significantly (P＜0.01), while serum insulin level of the group DM was decreased significantly(P＜0.01);compared with group DM, the above indexes were opposite in the group DE with intervention(P＜0.05). ③Compared with group C, the morphology of skeletal muscle cells in group DM was abnormal, the number of muscle nuclei was increased, the transverse lines were blurred and disappeared, the sarcomere was broken, and some muscle fibers were dissolved. Compared with group DM, the abnormal cell morphology, segmental injury of sarcomere and dissolution of muscle fibers in group DE were improved. The sarcolemma was more complete and the arrangement of muscle nuclei was more orderly. ④Compared with group C, the expressions of KLF15 and cleaved caspase-3, cells apoptosis rates in group DM were increased significantly(P＜0.01), while p-mTOR/mTOR level was decreased(P＜0.01) ; compared with group DM, the above indexes were opposite in the group with intervention(P＜0.05 or P＜0.01). Conclusion: Aerobic intermittent exercise is beneficial to improve the skeletal muscle pathological changes in type 2 diabetes rats, which may be due to the effective regulation of KLF15/mTOR related protein expression and the reduction of apoptosis damage.

О ЦЕЛЕСООБРАЗНОСТИ ПРОВЕДЕНИЯ ПОВТОРНОЙ РАДИОТЕРАПИИ ПРИ РЕЦИДИВАХ И ПРОДОЛЖЕННОМ РОСТЕ РАНЕЕ ОБЛУЧЕННЫХ ОПУХОЛЕЙ РАЗЛИЧНОЙ ЛОКАЛИЗАЦИИ

Introduction: The development of a recurrence or a second tumor in previously irradiated patients requires, in some cases, repeated radiotherapy (reirradiation) of the previously irradiated tissue volume. In the past decades, it was widely believed that it was possible to irradiate one anatomical zone in curative doses only once (taking into account the tolerance of healthy tissues) and the issue of repeated irradiation was practically not discussed (there are only a few studies). This approach was due to the fact that the use of old technologies did not allow sufficient protection of healthy tissues surrounding the tumor, which led to severe complications. Due to the development of radiotherapy technologies and new advances in radiobiology, the number of studies on the re-irradiation of recurrent tumors has recently increased significantly, however, they are mainly retrospective in nature and do not have a sufficient evidence compared to indications for primary radiotherapy. However, reirradiation can be used not only for palliative purposes, but also to achieve long-term local control. Modern medical approaches and technical capabilities make it possible to re-irradiate tumors of any localization, up to the second curative dose. Purpose: To investigate the expediency of repeated irradiation of patients with different tumor localizations, taking into account the survival rates of patients, possible complications and subsequent quality of life. Materials and methods: For the first time in Armenia, an analysis of the results of reirradiation is carried out on the basis of the experience of one clinic. The results of treatment of 1300 patients, who received radiotherapy at the IRA MEDICAL Group Radiotherapy Center from March 2019 to March 2022 were studied. The study included 52 patients, who received the second course of RT, which accounted for 4% of the total number of patients. The median age of patients was 60.5 years (22 - 81), including 22 men, 30 women, based on pathologies: CNS tumors - 17 patients, brain metastasis - 10, gynecology - 6, head and neck tumors - 6, metastatic skeletal bone lesions - 4, breast cancer - 3, other localizations - 6. Stage of the disease: III - 7 patients, IV - 37, unclassified - 8. The mean interval between two courses of radiotherapy was 34.5 months (1.5 - 252). The median total equivalent dose from two irradiation courses is 99 Gy (56-121). Except of the patients, who received reirradiation for metastatic relapse, the total equivalent dose was 102 Gy (84–121), and the median follow-up time after reirradiation was 9 months (4–29.5). Results: The average life expectancy of patients, who died during the observation period was 6.5 months (1-23). In 7 out of 52 patients, who initially had low KPS (60%), survival was up to 3.5 months or less. After excluding these patients from further statistical analysis, the median survival of the remaining patients was 10 months (4 – 23). As of March 31, 2022, 31 patients (59.6%) are alive, with an average follow-up of 13 months (5 – 29.5). The number of post-radiation complications and the quality of life of patients were also assessed. There were no treatment related deaths or reduced quality of life in the early stages. The results of this prospective study demonstrate that the use of the latest technologies in repeat radiotherapy can improve survival and quality of life in these patients. Thanks to new technologies, it is possible to conduct a repeated course of radiotherapy even in curative doses. When planning the second therapeutic or palliative course of radiotherapy, it is necessary to carefully select patients, taking into account a number of factors related to the previous treatment and the individual characteristics of the patient. After completion of the study, we plan to create recommendations on the criteria for selecting candidates for re-irradiation.

Bone metastases in prostate cancer - Gallium-68-labeled prostate-specific membrane antigen or Fluorine 18 sodium fluoride PET/computed tomography - the better tracer?

The objective was to assess the roles of 68Ga-PSMA PET/CT and 18F-NaF PET/CT in evaluation of skeletal metastatic lesions in prostate cancer. Two hundred consecutive prostate cancer patients who had undergone 68Ga-PSMA PET/CT and 18F-NaF PET/CT at baseline evaluation (n = 80) and following suspected recurrence or disease progression (restaging) (n = 120) were analyzed retrospectively. PSMA and NAF scans were positive for skeletal metastatic lesions in 67% (134 patients) and negative in 33% (66 patients). The scans were concordant in 80% (160 patients: 66 negative and 94 positive) and discordant in 20% (40 patients). Among 40 discordant results, 14 were baseline and 26 were restaging studies. PSMA detected more number of lesions in 11 (nine baseline and two restaging). These were true positive marrow or lytic metastatic lesions. NaF revealed more number of lesions in 29 (5 initial and 24 restaging). These were false positive on follow-up imaging. No statistical difference (P value = 0.7 by McNemar test) between the two scans for identifying absence or presence of at least one skeletal lesion was noted at baseline staging. Though, both 18F-NaF and 68Ga-PSMA are excellent tracers for evaluation of skeletal metastases in prostate cancer, there is a distinct advantage of 68Ga-PSMA PET/CT due to detection of additional skeletal lesions and absence of false positive lesions. In addition, absence of PSMA avidity in healed metastases in the restaging setting opens up new avenue for assessment of response of skeletal metastases.

Comparison of 18 F-PSMA-1007 PET/CT With 68 Ga-PSMA-11 PET/CT for Initial Staging in Intermediate- and High-Risk Prostate Cancer.

This study aimed to compare 18 F-PSMA-1007 PET/CT with 68 Ga-PSMA-11 PET/CT for initial staging in intermediate- and high-risk prostate cancer (PCa) patients. Forty treatment-naive, biopsy-proven, intermediate- or high-risk PCa patients were prospectively recruited. Each patient underwent PET/CT with 68 Ga-PSMA-11 and 18 F-PSMA-1007 (within 2 weeks). Assessment of both set of images included delineating number and characteristics of lesions, measurement of tracer uptake (SUV max ), miPSMA scoring, and PET-based stage categorization. Intraprostatic lesions were detected in all patients by both tracers with concordant PET-based T stage. Median SUV max of the dominant PSMA-positive prostatic lesions was not significantly different with 18 F-PSMA-1007 and 68 Ga-PSMA-11 (19.9 vs 19.4, P = 0.127, n = 40). Prostatic miPSMA scores were similar in 31/40 (77.5%) patients with both tracers (weighted κ = 0.71). In 23/40 (57.5%) patients, regional lymph nodes (n = 171) were detected by both tracers. Few additional PET-positive regional lymph nodes (n = 3) were exclusively detected by 18 F-PSMA in 2 patients without altering PET-based N stage. Extraregional lymph nodes (n = 123 in 17/40 patients) and visceral metastatic lesions (n = 18 in 3/40 patients) were detected concordantly by both tracers. PET-positive marrow based and skeletal metastases (n = 71) were detected in 14/40 (35%) patients by both tracers. Few additional marrow and skeletal lesions (n = 7) were exclusively detected on 18 F-PSMA-1007 in 5/14 patients, potentially upstaging PET-based M stage in 2/5 patients. Both radiotracers showed excellent interreader agreement for region-wise detection of lesions. Our results suggest that 18 F-PSMA-1007 PET/CT is comparable to 68 Ga-PSMA-11 PET/CT in detecting primary and metastatic lesions of PCa.

Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease.

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM cells arehighly glutamine addicted. Interestingly, these metabolic changes in MM cells may affect BM microenvironment cells by altering the differentiation process of osteoblasts from mesenchymal stromal cells. The identification of glutamine metabolism alterations in MM cells and bone microenvironment may provide a rationale to design new therapeutic approaches and diagnostic tools. The osteolytic lesions are the most frequent clinical features in MM patients, often characterized by pathological fractures and acute pain. The use of the newer imaging techniques such as Magnetic Resonance Imaging (MRI) and combined Positron Emission Tomography (PET) and Computerized Tomography (CT) has been introduced into clinical practice to better define the skeletal involvement. Currently, the PET/CT with 18F-fluorodeoxyglucose (FDG) is the diagnostic gold standard to detect active MM bone disease due to the high glycolytic activity of MM cells. However, new tracers are actively under investigation because a portion of MM patients remains negative at the skeletal level by 18F-FDG. In this review, we will summarize the existing knowledge on the metabolic alterations of MM cells considering their impact on the BM microenvironment cells and particularly in the subsequent formation of osteolytic bone lesions. Based on this, we will discuss the identification of possible new druggable targets and the use of novel metabolic targets for PET imaging in the detection of skeletal lesions, in the staging and treatment response of MM patients.

P008: Impact of bone marrow involvement on early PET response and progression-free survival in the HD18 trial for patients with advanced-stage Hodgkin lymphoma

Background: The prognostic role of bone marrow (BM) involvement in advanced-stage Hodgkin lymphoma is unclear, particularly for patients receiving intensive first-line treatment. We thus retrospectively examined its impact on early response and progression-free survival (PFS) among individuals receiving escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) in the HD18 trial. Patients and Methods: A total of 424 individuals were suitable for analysis, of which 124 (29%) had BM involvement according to initial positron emission tomography (PET). Patient outcome was measured by PET response after 2×eBEACOPP and five-year PFS rate. Results: After 2×eBEACOPP, 79 of the BM PET-negative individuals (26%) and 26 of the BM PET-positive patients (21%) were found to be PET-positive (odds ratio [OR] 0.74, P=0.25). The five-year PFS rate was 90.7% in BM PET-negative individuals and 91.8% for BM PET-positive patients (hazard ratio 0.82, P=0.6). In our BM PET-positive subgroup, nine (16%) of the 56 subjects with one or two sites of skeletal uptake were PET-positive after 2×eBEACOPP as compared to 17 (25%) of the 68 individuals showing three or more BM lesions (OR 1.74, P=0.23). Conclusions: The present analysis demonstrates that BM involvement, irrespective of its extent, does not lead to increased risk for a positive interim PET result or inferior PFS in advanced-stage Hodgkin lymphoma patients undergoing eBEACOPP treatment. Skeletal lesions cannot therefore be considered as an additional prognostic marker of therapy failure or disease recurrence for individuals receiving intensive first-line treatment.

The subtalar calcaneal angle: A novel angle for evaluation of displaced calcaneal fractures – A retrospective study

ObjectivesThe radiological measurement of the Böhler angle (BA) and the critical angle of Gissane (CAG) is used not only to diagnose and corroborate the suspicion of the presence of calcaneal fractures but also to assess the prognosis of different injury patterns and to evaluate the operative reduction of calcaneal fractures. Notwithstanding, many previous studies indicated the poor intra- and interobserver reproducibility of both angles. In this retrospective study, we present the subtalar calcaneal angle (SCA) as an additional diagnostic tool -to BA and CAG-which can be applied on pre- and postoperative radiographs to assess calcaneal fractures involving the posterior facet. DesignRetrospective Study. MethodsTwo retrospective groups were established, a ‘CF-group’ including radiographs of patients diagnosed with a calcaneal fracture and underwent operative treatment in the authors' traumatology department, and a ‘control group’ with 50 lateral calcaneal radiographs clear of skeletal lesions. Initially, the SCA, BA, and CAG were measured in both groups by three examiners. Those measurements were repeated one month later. The intra- and intertester reliabilities of all three angles were tested by determining the intraclass correlation coefficient (ICC). A paired t-test was used to prove the statistically significant difference between the SCA values for the pre- and postoperative groups, while the significant difference between the SCA values for the control and preoperative groups was tested through an independent-samples t-test. ResultsThe intra- and interobserver reliability of the SCA and the BA was in close proximity. The values of the SCA in both the control and postoperative groups were significantly different compared to the measurements of the preoperative group. The CAG showed poor intertester reliability. ConclusionThe subtalar calcaneal angle is a new instrument with proven reliability in estimating the prognosis of displaced calcaneal fractures and the postoperative alignment of the posterior facet. Level of clinical evidenceDiagnostic, Level III.

Langerhans Cell Histiocytosis: A Population-based Study of Anatomical Distribution and Treatment Patterns

BackgroundLangerhans cell histiocytosis (LCH) is a rare monoclonal histiocytic neoplasm. Little is known about clinical factors associated with LCH single- vs multi-system involvement at the time of diagnosis. MethodsData on 1549 LCH patients diagnosed between years 2010 and 2018 were extracted from the Surveillance, Epidemiology and End Results Program. Patterns of single- vs multisystem involvement were examined using multivariable logistic regression analysis. Odd ratio (OR) and 95% confidence interval (CI) were reported. Results968 children and adolescents (0–19 years; median: 4 years) and 581 adults (≥20 years; median: 49 years) were included in the analysis. Multi-system LCH was reported for 30.9 % patients. Bone marrow (BM) (OR = 3.776; 95 %CI = 1.939–7.351; P < 0.001) and lymph node (LN) (OR = 3.274; 95 %CI = 1.443–7.427; P = 0.005) involvement were most commonly associated with multi-system LCH at the time of diagnosis; similar pattern was also observed in adult patients (OR = 17.780; 95 %CI = 6.469–48.867; P < 0.001 for BM LCH; and OR = 5.156; 95 %CI = 2.131–12.471; P < 0.001 for LN LCH). Among pediatric patients, craniofacial osseous LCH was more likely to be treated with surgery (OR = 2.822; 95 %CI = 1.199–6.639; P = 0.018) compared to skeletal lesions in other sites, whereas vertebral body LCH was less likely to be treated with surgery (OR = 0.175; 95 %CI = 0.058–0.527; P = 0.002). In pediatric patients with bone LCH, the non-white patients were less likely to be treated surgically compared to the white patients (OR = 0.470; 95 %CI = 0.272–0.812; P = 0.007). ConclusionsBM and LN LCH are associated with the highest risks of multi-system disease, which may require active surveillance. Furthermore, active attempts are needed to mitigate the racial disparity in surgery utilization in pediatric patients with skeletal LCH.

Update on Current Imaging of Systemic Lupus Erythematous in Adults and Juveniles.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and organ systems. Musculoskeletal (MSK) involvement is one of the most frequent and the earliest locations of disease. This disease affects joints and periarticular soft tissues, tendon sheaths and tendons, bones, and muscles. Multimodality imaging, including radiography, ultrasound (US), and magnetic resonance imaging (MRI), plays a significant role in the initial evaluation and treatment follow up of MSK manifestations of the SLE. In this paper, we illustrate MSK imaging features in three clinical forms of SLE, including nondeforming nonerosive arthritis, deforming nonerosive arthropathy, and erosive arthropathy, as well as the other complications and features of SLE within the MSK system in adults and juveniles. Advances in imaging are included. Conventional radiography primarily shows late skeletal lesions, whereas the US and MRI are valuable in the diagnosis of the early inflammatory changes of the soft tissues and bone marrow, as well as late skeletal manifestations. In nondeforming nonerosive arthritis, US and MRI show effusions, synovial and/or tenosynovial hypertrophy, and vascularity, whereas radiographs are normal. Deforming arthritis clinically resembles that observed in rheumatoid arthritis, but it is reversible, and US and MRI show features of inflammation of periarticular soft tissues (capsule, ligaments, and tendons) without the pannus and destruction classically observed in RA. Erosions are rarely seen, and this form of disease is called rhupus syndrome.