Skeletal Survey Research Articles

Diagnostic testing for and detection of physical abuse in infants with brief resolved unexplained events

BackgroundA Brief Resolved Unexplained Event (BRUE) can be a sign of occult physical abuse. ObjectivesTo identify rates of diagnostic testing able to detect physical abuse (head imaging, skeletal survey, and liver transaminases) at BRUE presentation. The secondary objective was to estimate the rate of physical abuse diagnosed at initial BRUE presentation through 1 year of age. Participants and settingInfants who presented with a BRUE at one of 15 academic or community hospitals were followed from initial BRUE presentation until 1 year of age for BRUE recurrence or revisits. MethodsThis study was part of the BRUE Research and Quality Improvement Network, a multicenter retrospective cohort examining infants with BRUE. Generalized estimating equations assessed associations with performance of diagnostic testing (adjusted odds ratio (aOR)). ResultsOf the 2036 infants presenting with a BRUE, 6.2 % underwent head imaging, 7.0 % skeletal survey, and 12.1 % liver transaminases. Infants were more likely to undergo skeletal survey if there were physical examination findings concerning for trauma (aOR 8.23, 95 % CI [1.92, 35.24], p < 0.005) or concerning social history (aOR 1.89, 95 % CI [1.13, 3.16], p = 0.015). There were 7 (0.3 %) infants diagnosed with physical abuse: one at BRUE presentation, one <3 days after BRUE presentation, and five >30 days after BRUE presentation. ConclusionThere were low rates of diagnostic testing and physical abuse identified in infants presenting with BRUE. Further study including standardized testing protocols is warranted to identify physical abuse in infants presenting with a BRUE.

Increased severity of abusive head trauma during the first year of the COVID-19 pandemic

BackgroundAbusive head trauma (AHT) is the leading cause of death from physical abuse in children. Reports regarding the impact of the COVID-19 pandemic on rates and severity of AHT are limited and with conflicting results. ObjectiveTo determine the number and clinical characteristics of AHT cases presenting to a pediatric tertiary care center during the first year of the COVID-19 pandemic compared to the two prior years. Participants and settingWe performed a retrospective cohort study of patients <5 years old diagnosed with AHT at a single pediatric tertiary care center over a three-year period. MethodsData were obtained for the pandemic year and two years before, including demographics, length of stay, physical and retinal examination findings, radiologic studies, electroencephalogram results, and mortality. ResultsThere were 27 cases of AHT during the first year of the pandemic and 55 during the two pre-pandemic years. Length of stay was similar for the two cohorts. The mortality rate was higher during the pandemic (29.6 % vs. 3.6 %; p < .01), as were the proportion of patients with retinal hemorrhages (84.6 % vs. 41.5 %; p < .01) and abnormal cervical spine imaging (52.6 % vs. 21.2 %; p = .02). There were no differences in age, sex, race, abnormalities on dermatological exam, skeletal surveys, and electroencephalograms. ConclusionsWe did not observe an increase in the number of patients with AHT during the pandemic but did see an increase in mortality, patients with retinal hemorrhages, and patients with abnormalities on cervical spine imaging. These data suggest a higher severity of AHT presenting to a pediatric tertiary care center during the pandemic.

IgD Multiple Myeloma, Does It Still Have a Poor Prognosis?

IgD Multiple myeloma is considered unusual myeloma, with just 2% of cases of MM being diagnosed as IgD subtype. The infrequency of its presentation and the poor prognosis make the disease challenging to treat, with many patients being selected for clinical trials. A 63-year-old female presented to the ER after falling on ice. After undergoing a CT Head, multiple lytic lesions in the occipital region were found, confirmed by MRI. 2 months later, a bone marrow biopsy found 90% of marrow replaced by CD138 plasma cells, positive for kappa & negative for lambda, consistent with myeloma. On evaluation, she was found to have pan-hypo-gammglobulinemia. However, the skeletal survey did not find any other lytic lesions. Seeing this, IgD levels were measured and found to be >100 times over the upper normal limit with normal beta2-microglobulin levels, confirming monoclonal gammopathy. A FISH study found the patient positive for t(11;14)/CCND1IGH translocation (85% of cells) and negative for TP53. Palliative radiotherapy for the skull base was performed before the patient started chemotherapy. The patient was deemed a suitable candidate, selected for a clinical trial, and placed on RVd [revlimid + velcade + dexamethasone] with delayed bone marrow transplant. As the patient developed a rash and neuropathy from velcade [bortezomib], it was paused and restarted after three months. The patient was doing well on this chemotherapy regimen for two years and was placed on lenalidomide-based maintenance therapy. Two years later, her disease started progressing with an increased frequency of bone pains and opioid dosing. At this juncture, it was decided to change course and start her on pomalidomide/dexamethasone. This did not help the patient, and the neurological side effects of dexamethasone made us change course and initiate a daratumumab, bortezomib, cyclophosphamide and dexamethasone. This proved unfruitful, too, as the patient developed adverse effects of polyneuropathy, pancytopenia requiring transfusion, and worsening GERD. Seeing the disease relapse and intolerance to the previous regimen, we decided to initiate a once-per-week regimen of selinexor, bortezomib, and dexamethasone. The patient has improved on this regimen and is back to her baseline for physical activity, mental status and pain, and an improved appetite. In this case, we wanted to highlight how incidental findings on a CT lead us to diagnose a rare type of multiple myeloma and how, in the era of novel agents, the survival of patients can be prolonged significantly. Considering the rarity of this subtype, international collaborative studies are suggested to further elucidate the underlying mechanisms for developing potent therapeutic approaches. Most of the data reported on how IgD multiple myeloma progresses was written before the arrival of novel agents. More evaluation of survival times and progression of the disease needs to be done as it's possible that IgD MM is not as poor a prognosis as it once was.

A case of McCune–Albright syndrome hiding in the bones

McCune–Albright syndrome (MAS) is a rare genetic disorder which presents across a broad clinical spectrum. The characteristic features are café-au-lait macules, fibrous dysplasia of the bone (FD), and hyperfunctioning endocrinopathies. A 10-year-old girl presented with peripheral precocious puberty, growth hormone (GH) excess, and asymptomatic FD without café-au-lait macules. MAS should be suspected in the presence of any characteristic feature, even in the absence of café-au-lait macules. A skeletal survey should be considered in patients presenting with an unknown cause of peripheral precocious puberty to search for signs of FD, even in the absence of other clinical manifestations.

Enhanced Global Disease Assessment with Advanced Imaging and Targeted Myeloma Lesion Biopsy Highlights Spatial Heterogeneity and Detects Residual Disease in Multiple Myeloma

Background: Multiple myeloma (MM) is a biologically complex disease with marked heterogeneity; limitations remain in our standard myeloma disease assessment at diagnosis and in response to therapy. In this study, we aimed to prospectively investigate the utilization of advanced imaging and targeted focal lesion (FL) biopsies to augment global disease evaluation, detect residual tumor burden, and explore the diverse histologic and molecular landscape of this multifocal neoplasm. Herein, we present our final analysis of this clinical trial. Methods: Adult patients with newly diagnosed clinical MM (NDMM) and bone or extramedullary (EM) FL were eligible to participate in this prospective study. Advanced imaging with positron emission tomography/computed tomography (PET/CT) or whole body magnetic resonance imaging (WB-MRI), standard bone marrow (BM) biopsy and aspiration, and targeted FL biopsy were performed at enrollment and after four 28-day cycles of induction therapy with carfilzomib (36 mg/m2 intravenously twice weekly), lenalidomide (25 mg orally days 1-21), and dexamethasone (40 mg orally weekly) (KRd), with dose modifications as needed. Conventional clinical response, using IMWG Response Criteria (Kumar S et al, 2016), was also measured after each cycle of treatment. Patients were followed for 12 months after end of treatment or until data cutoff on February 23rd, 2022. Results: 27 patients were enrolled in this study between June 2018 and August 2021, with 25 evaluable for global response assessment. Median age was 61 years (range, 42-76 years) and 14.8% of patients were of Black or African American race. 85.2% of patients had Revised International Staging System (R-ISS) stage II or III disease. 51.9% of patients were identified as having EM disease arising out of bone or soft tissue and 44.4% of patients had high risk cytogenetics inclusive of chromosome 1 abnormalities. In sum, 70.4% of our cohort had at least 1 high risk feature at diagnosis (Table 1). 80% of patients had myeloma FL identified on advanced imaging that were missed on conventional skeletal survey. Of the 7 patients with cytogenetic and fluorescence in situ hybridization (FISH) testing performed on initial FL biopsy, 6 (85.7%) had findings discrepant from those seen on cytogenetic testing from standard BM samples. 9 patients had cytogenetic and FISH studies on repeat myeloma FL biopsy after KRd induction with 2 showing residual FISH abnormalities that were not detected on standard BM obtained for response assessment. Clinical response rates after 4 cycles of KRd were high in our study population with 88% of patients achieving a very good partial response (VGPR) or better and 20% with a stringent complete response (sCR) with minimal residual disease (MRD) negativity by flow cytometry. However, of the 22 patients with ≥VGPR by IMWG response assessment, 18 had residual disease on advanced imaging with WB-MRI (10 patients), PET/CT (7 patients), or MRI total spine (1 patient), including 3 of the 5 patients with sCR (Figure 1). 2 patients experienced disease progression during the study period with median progression free survival not reached by the patient cohort. Both patients with progression had a VGPR by conventional response assessment, though with residual FL on advanced imaging post-KRd induction. Conclusions: While tumor spatial differences in MM have been observed retrospectively, prospective data on this important component of myelomagenesis is limited. In our cohort of high risk NDMM, we demonstrated spatial heterogeneity both at diagnosis and after KRd induction. Despite the deep clinical responses observed by IMWG response assessment, 81.8% of patients with ≥VGPR had ongoing abnormalities on advanced imaging which could potentially serve as disease reservoirs for future progression and development of treatment resistance. A novel assessment method in MM, inclusive of advanced imaging and targeted FL biopsies, may overcome the limitations of our standard response assessment with resultant improved knowledge of the varied intra-tumor disease biology as well as development of more refined treatment approaches. A potential limitation of our study is the smaller sample size with underrepresentation of minority populations. Data on whole exome sequencing of paired BM and FL biopsies will be reported separately. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Approach to the Patient With Short Stature: Genetic Testing.

The first step in the evaluation of the short child is to decide whether growth parameters in the context of the history are abnormal or a variant of normal. If growth is considered abnormal, system and hormonal tests are likely to be required, followed by more directed testing, such as skeletal survey and/or genetic screening with karyotype or microarray. In a small percentage of short children in whom a diagnosis has not been reached, this will need to be followed by detailed genetic analysis; currently, exome sequencing using targeted panels relevant to the phenotype is the commonly used test. Clinical scenarios are presented that illustrate how such genetic testing can be used to establish a molecular diagnosis, and how that diagnosis contributes to the management of the short child. New genetic causes for short stature are being recognized on a frequent basis, while the clinical spectrum for known genes is being extended. We recommend that an international repository for short stature conditions is established for new findings to aid dissemination of knowledge, but also to help in the definition of the clinical spectrum both for new and established conditions.

KNOWLEDGE AND PRACTICE OF IMAGING OF CHILDREN WITH SUSPECTED CASES OF NON-ACCIDENTAL INJURIES AMONG RADIOGRAPHERS WITHIN MAIDUGURI METROPOLIS, NORTHEASTERN NIGERIA

Objectives: To assess the knowledge and practice of Non-accidental injuries (NAI) among radiographers practising within Maiduguri Metropolis. Methods: A cross-sectional study was conducted using a questionnaire to elicit information on knowledge and practice of imaging children with Non-accidental injuries. The information elicited from the questionnaire related to the following themes: Demographic characteristics, knowledge and practice of imaging children with NAI. Informed consent was sought from participants. Descriptive statistics (mean, frequencies) were used to analyze the data. Results: A total of 45 questionnaires were distributed to radiographers, and 36 (100%) were completed and returned. A total of 23 (63.9%) were males and 13 (36.1%) were females. The majority 34 (94.4%) of the respondents had good knowledge of NAI. Skeletal survey was the examination commonly requested in children with NAI as reported by 23 (63.9%) respondents, and the majority of the participants 31 (86.1%) had no speciality training in pediatric imaging. A total of 23 (63.9%) participants knew that using a single film to image the whole body (baby-gram) was an obsolete examination. Conclusion: Radiographers in this study have good knowledge of NAI in children and are involved in imaging children with suspected cases of non-accidental injury. It is evident from the results of this study that NAI among children occurs in our environment and a majority of these cases are underreported and may even go unnoticed. Having adequate knowledge of clinical and radiologic manifestations of NAI in children will enable the radiographer to deliver evidence-based practice in line with international best practices.

PSAT180 Fibrodysplasia Ossificans Progressiva (FOP) A Case Series

Abstract Case 1 (TTD 30yrs): 71-year-old female presented with decreased mobility over the past 15years. She had malformations of the great toes. She developed "golf ball" sized calcified lumps in the upper ribs, clavicle and sternum which began to form at the age of 32 and were removed surgically. Calcified soft tissue was noted over the shoulders, spine and thighs. No history of hearing impairment. Radiographs showed areas of abnormal bone growth. CT scan of abdomen showed calcifications within the gluteal and thigh muscles The lab profile was normal. DNA analysis in process.Case 2 (TTD 13yrs): A 53-year-old female with symmetric malformations of the great toes presented with a lump behind her knee in her 40's with histopathology consistent with calcium deposition. She was diagnosed initially with dermatomyositis and treated with steroids. No hearing impairment The lab profile and abdominal CT scan were unremarkable. DNA analysis in the process.Case 3: (TTD 25yrs) A 66 yr old female presented with multiple lesions of heterotopic ossification lesions which began at the age of 41 at sites of trauma in the right deltoid, right hip, right calf. These were surgically removed. Also had a malformation of the great toes bilaterally. Received radiation post excision of the calcified lesion in April 2021. A skeletal survey showed myositis ossificans. DNA analysis in the process.

PMON110 Panhypopituitarism as a Rare Presentation of Erdheim – Chester disease (ECD) in an Adolescent Patient

Abstract Background Erdheim-Chester disease (ECD) is a rare multisystemic histiocytic disorder. Only a dozen pediatric cases are reported. Here, we present a case of ECD in a pediatric patient who presented with short stature and delayed puberty. Clinical Case A 14-year-old male with history of autism and ADHD presented with short stature and pubertal delay. He grew along the 40th percentile until age 7 years when growth velocity declined. On exam, his height was 145.6 cm (0.98%ile, z-score -2.34), weight was 55.6 kg (63.19%ile, z-score 0.34), and testicular size was 5-6 mL. He had increased thirst and episodes of bedwetting since age 7. Bone age was delayed at 11 years 6 months. Further workup was recommended, but family was lost to follow up. At 16, he returned with continued poor growth, polydipsia, and nocturia. Height was 153 cm (0.26%ile, z-score -2.80), weight 61.1 kg (40%ile, z-score -0.25). Labs revealed IGF-BP3 2.8mcg/mL(3.1-8.9), IGF-1 35ng/mL(245-522), LH 1.2mIU/mL(0.29-4.77), and total testosterone &amp;lt;7.0 ng/dL(250-1100). Prolactin, cortisol, thyroid, and karyotype were normal. Growth hormone (GH) stimulation test confirmed GH deficiency. He was referred to oncology clinic when a brain MRI revealed a nodular enhancing suprasellar mass extending from the third ventricular floor to the dorsum sella along the pituitary stalk and rounded sclerotic lesion in the frontal bone. Biopsy of the suprasellar lesion was remarkable for foamy histiocytes positive for CD68, negative for S100 and CD1a, an eosinophilic cell background highlighted by S100 and synaptophysin, SALL4 negative. A diagnosis of xanthomatous hypophysitis was made. Additionally, lab studies confirmed diabetes insipidus (DI), treated with DDAVP. Growth hormone was trialed for 2 weeks, but he developed acute pancreatitis, so it was discontinued. He subsequently developed recurrent pancreatitis of unclear etiology requiring frequent hospitalization with development of insulin-dependent diabetes mellitus due to pancreatic damage. He was lost to follow up for 12 months after leaving home at age 18. He returned to our institution after incidental findings of 7th right rib expansile lytic bony lesions on abdominal CT during a pancreatitis admission. Biopsy of the rib lesion was positive for a BRAF-V600E mutation. Skeletal survey revealed new multiple small lytic skull lesions. Repeat brain MRI demonstrated new calvarial lesions, increased suprasellar mass. Chest CT scan showed a micronodular pattern with mediastinal lymph node enlargement. PET confirmed widespread multifocal FDG hypermetabolic lesions. Final diagnosis of ECD was made; he was started on targeted therapy with Vemurafenib, a BRAF inhibitor. Conclusion Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis, which rarely affects pediatric patients who present with bone pain and DI; however, here we present a case of ECD in an adolescent with short stature and multiple pituitary deficiencies to highlight the varied presentation of the disorder. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBODP018 Hypercalcemia In A Child On Ketogenic Diet For Intractable Epilepsy

Abstract Introduction Ketogenic diets have been shown to significantly reduce seizures in patients with intractable epilepsy refractory to common antiepileptic medications. There have been reports of hypercalcemia in diet-controlled epilepsy patients. The exact cause of hypercalcemia in ketogenic diets is unclear but decreased bone formation and impaired calcium excretion are suggested mechanisms. Case An 8-year-old male with Lennox-Gastaut syndrome was noted to have incidental hypercalcemia on admission (serum calcium 11.5 mg/dL, n = 8.8-10.1) for aspiration pneumonia, UTI, and increased seizure-like activity. Hypercalcemia persisted throughout his hospitalization (range: 10.8-12.4 mg/dL). Evaluation of hypercalcemia indicated normal serum phosphate (5.6 mg/dL, n = 3. 0-6. 0), appropriately low PTH (9.5 pg/mL, n = 10. 0-65. 0), undetectable PTHrP (&amp;lt;2. 0 pmol/L), low 25 (OH) vitamin D (19ng/ml, n=30-100), low 1,25 (OH)2 vitamin D (7.1 pg/mL, n = 19.9-79.3), normal creatinine (0.3 mg/dL, n = 0.31-0.61), slightly elevated TSH (5.13 mIU/L, n = 0.5-4.5) with a normal free T4 (1.4 ng/dL, n = 0.8-2. 0), and physiologic CBC. Alkaline phosphatase was low (88 U/L, n = 156-386) and skeletal survey showed diffuse demineralization. Urine calcium creatinine ratio was elevated at 0.6 when serum calcium was 11.6 mg/dl. Patient was 7 months into a ketogenic diet that successfully reduced seizure frequency and the plan was to further intensify the diet. On hospital day 11 when serum calcium was 12mg/dl, he was started on IV normal saline and furosemide up to a daily dose of 60 mg. On hospital day 12, patient was started on calcitonin (3 U/kg twice daily SQ). Serum calcium normalized (10 mg/dl), but calcitonin had to be discontinued due to severe nausea and vomiting. GI symptoms did not improve on a lower calcitonin dose. Calcium gradually corrected on fluids and furosemide, but hypercalcemia recurred (11mg/dl) after furosemide was weaned. The patient was then transferred to a higher level of neurologic care to continue treatment and increase the intensity of the ketogenic diet. There, on cumulative hospital day 26, he received zoledronic acid (0. 0125 mg/kg) which was tolerated well and resulted in normalization of the serum calcium levels (10.9mg/dl, 10.2mg/dl and 9.8mg/dl on days 26, 28 and 29 respectively). Conclusions This case adds to the limited literature available on the evidence that management of refractory epilepsy with ketogenic diets may cause acute hypercalcemia. Although the underlying cause is unclear, decreased osteogenesis as marked by low alkaline phosphatase activity remains the likely explanation. Other risk factors such as immobilization also need to be explored. The successful implementation of protocols used to treat our patient and similar patients in the literature may help create screening protocols for early detection and management of the hypercalcemia to prevent complications. Presentation: No date and time listed

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.

PMON306 A Multisite Study Evaluating Frequency and Characteristics of Non-Ossifying Fibromas in Children with Congenital Forms of Rickets.

Abstract Purpose Non-ossifying fibromas (NOF) are benign, fibrous lesions of the skeleton estimated to occur in about 30% of children and adolescents. In the general pediatric population, they are twice as common in males, usually asymptomatic and self-limiting. Etiology is largely unknown, though multiple NOF are described with genetic syndromes such as neurofibromatosis 1. We have observed NOF in children with various forms of rickets. However, there is limited information on the frequency and characteristics of NOF in rickets. The purpose of this study was to evaluate the frequency of NOF in various congenital forms of rickets under care in tertiary care centers and describe their characteristics. Methods This was a retrospective chart review of patients with congenital forms of rickets and at least one bilateral lower extremity radiograph taken between 4 and 18 years of age at two academic children's hospitals in the United States and Canada between 2004 to 2020. Rickets diagnosis was confirmed by clinical, biochemical, radiographic, and genetic testing where available. Data are described as proportions and percentages for categorical variables and means with standard deviations for continuous variables. Results Sixty-four patients, mean age 13.3 ± 5.1 years old (66%F, 46% Hispanic) were included with the following diagnoses: X-linked Hypophosphatemia (XLH, n=55, 86%), renal hypophosphatemia [n=4, 6% (3 Fanconi syndrome, 1 Dent disease)], hereditary vitamin D resistant rickets (HVDRR, n=3, 5%), and hereditary vitamin D dependent rickets type 1 (VDDR1, n=2, 3%). Fifteen patients (23%, 67%F) had at least one NOF, of whom 13 (87%) had XLH, one (7%) had HVDRR, and one (7%) had VDDR1. All NOF were localized to the lower extremities (60% femur, 27% tibia, and 13% fibula); there were no NOF in the upper extremities or at other sites among those with relevant skeletal imaging (n=32 with upper extremity and/or full skeletal survey data). The mean NOF height was 24.1 ± 13.8 mm and width 10.1 ± 5.3 mm. Nine of 15 patients with NOF (60%) compared with 21/49 without NOF (43%) required angular deformity surgery. Three patients (20%) experienced fractures within the lesions, two (13%) had two lesions each, and one (7%) had a progressive lesion requiring surgery with grafting. Conclusion We describe the frequency of NOF in children with congenital forms of rickets followed in academic centers. NOF were identified in almost a quarter of patients, and patients with NOF required angular surgery more often. Fractures were present within the lesions in one fifth of those with NOF, suggesting clinically important osteomalacia at that site. Interestingly, in contrast to the general pediatric population, we found no male preponderance. Long-term follow up and future studies are important to further characterize NOF in various forms of rickets, their pathogenesis, progression, and association with the disease severity. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP132 Efficacy of Romosozumab for Osteoporosis in a Patient with Hajdu-Cheney Syndrome: A Case Report

Abstract Introduction Hajdu–Cheney syndrome (HCS) is a genetic disease with an autosomal-dominant pattern caused by mutations of NOTCH2. This rare disease primarily causes skeletal dysplasia, including craniofacial dysmorphology, dental anomalies, and short stature accompanied by radiographic abnormalities with acroosteolysis and generalized osteoporosis. Even if a definite diagnosis of HCS could be reached as techniques for genetic testing have been advanced, the more important problem is that there is no effective pharmacological treatment for this disease at present. In this study, we aimed to evaluate the efficacy of romosozumab for improving bone fragility in our osteoporotic HCS patient. Clinical Case Report A 43-year old woman was referred to our department to evaluate skeletal dysplasia. She underwent surgical correction of valvular disease when she was 11 years old. She did not have any fracture before she was 26-years old when she got an L1 compression fracture while carrying heavy stuff. She presented with persistent pain and progressive shortening of both fingers and toes since she was 29-years old. She also has hearing difficulty. Physical examination revealed coarse facial features such as micrognathia, low-set ears, elongated philtrum, bushy eyebrows, the wide nose and short digits showing pseudo-clubbing. There were no abnormalities in her biochemical results for liver and renal function, serum calcium, phosphate, alkaline phosphatase, thyroid-stimulating hormone, estradiol, parathyroid hormone, and 25-hydroxy vitamin D. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry showed T score of -4.2, -2.4, and -1.5 at the lumbar spine (LS), femur neck (FN), and total hip (TH), respectively. A skeletal survey revealed acro-osteolysis and deformity of all digits bilaterally and compression fracture at T8, T10, and L1. Her next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G&amp;gt;A, leading to Trp2253Ter amino acid in NOTCH2 gene annotated as pathogenic. Romosozumab treatment (210mg injected subcutaneously every month) with calcium and vitamin D supplements was started because she had already received bisphosphonate for 10 years without preventing progressive osteolytic lesions and repeated fractures. After one year of treatment with romosozumab, BMD increased by 15.4%, 6.3%, and 1.3% to T-score of -3.5, -2.1, and -1.4 at LS, FN, and TH, respectively. Overall, C-telopeptide was suppressed by 26.4%, 0.121 to 0. 089 ng/mL, and P1NP was increased by 18.7% from 25.2 to 29.9ng/mL with transient fluctuation during the follow-up period. Follow-up radiographs of the hand and feet showed no progressive acro-osteolysis. Clinical conclusion: This is the first treatment report of romosozumab for an osteoporotic HCS patient in Korea. One year of romosozumab treatment provided substantial gains in BMD and prevented progressive acroosteolysis, which represents a promising treatment option for the rare disease of HCS. Presentation: No date and time listed

PSAT219 Renal Phosphate Wasting Caused by ENPP-1 mutation.

Abstract Background Increased renal phosphate loss can be Fibroblast Growth Factor-23 (FGF-23) dependent or independent. FGF-23 reduces expression of Sodium-Phosphate co-transporters, responsible for phosphate reabsorption; and by inhibition of 1-alpha hydroxylation of 25-OH-D3. Reduced serum concentration of 1, 25-OH2-D3 results in secondary hyperparathyroidism. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) mutation is one of the rarest causes of hypophosphatemia, which causes FGF-23 dependent hypophosphatemia. Case description 31-year-old female referred to endocrinology for evaluation of recurrent nephrolithiasis despite normalization of PTH and serum Calcium (Ca) after right inferior parathyroid adenoma resection. Repeated renal stone analysis revealed calcium phosphate as the major stone composition. Patient achieved mid parental height, denied history of calcium or phosphate metabolism disorders/ rickets in the family. Physical exam was not suggestive of rickets and skeletal survey showed normal bone mineralization. Initial labs following parathyroid adenoma resection showed normal Ca 9.7 mg/dl, PTH 47 pg/ml, Phosphorus (Ph) 2.3 mg/dl, 25-OH-D3 51 ng/ml, albumin 3.9 g/dl, Mg 1.8 mg/dl. Repeat fasting labs six months later revealed Ca 9 mg/dl, Ph 1.7 mg/dl, 25-OH-D3 52 ng/ml, PTH 67.5 pg/ml and albumin 3.7 g/dl. Persistent low serum phosphate was evaluated further by a 24-hour urine collection which revealed high urine phosphate of 828 mg/day, Ca 181 mg/day, Mg 23 mg/day and creatinine was 1485 mg/day. Tubular reabsorption of phosphorus was 77% (normal: &amp;gt;80%), indicating renal phosphate wasting. Serum FGF-23 on two different days was &amp;gt;180 RU/ml. Next-generation sequencing tested positive for heterozygous ENPP-1 gene mutation variant c1441C&amp;gt;T (p. Arg481Trp). Patient was started on oral Phosphorus supplementation &amp; calcitriol. Repeat labs showed normalization of Ph 2.4 mg/dl. Audiology evaluation suggested mild sensorineural hearing loss. Heart calcium score was zero. Discussion ENPP1 gene mutation's clinical presentations can vary from no symptoms, hypophosphatemic rickets to death in the first six months of life from generalized arterial calcification. ENPP1 is an enzyme, which degrades ATP into adenosine monophosphate (AMP) and pyrophosphate (PPi). PPI is an inhibitor of hydroxyapatite crystallization in vascular tissue and organs, while Ph is a pro-mineralization factor. ENPP1 gene mutation results in a low concentration of PPi, predisposing the patient to pathological calcification. It is speculated that ENPP-1 modulates FGF-23 secretion. FGF-23 elevation in these patients is a protective response, as hypophosphatemia prevents pathological calcification. Treatment target is to keep phosphate at low end of normal. In our patient, ENPP- 1 mutation likely contributed to recurrent renal stones and possible parathyroid adenoma. Evaluation of genetic mutations is necessary to decide for or against FGF-23 antibody/Burosumab treatment. In ENPP-1 mutation. Burosumab should be avoided as it can bind to FGF-23 resulting in pathological calcification. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The added value of skeletal surveys in the initial evaluation of children diagnosed with Langerhans cell histiocytosis in the era of staging 18 F-FDG PET/CT: A retrospective study.

Currently, there is no consensus protocol on the initial staging evaluation for Langerhans cell histiocytosis (LCH). Our institutional protocol consists of a skeletal survey and a whole-body positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (FDG PET/CT) study. The utility of the PET/CT lies in its sensitivity in detecting osseous and extra-osseous lesions, and in determining the baseline metabolic activity of LCH lesions to assess treatment response. However, the added utility of the skeletal survey in staging LCH is unclear. Therefore, this study retrospectively assessed the added diagnostic value of skeletal surveys in patients with baseline PET/CTs for initial staging of LCH. We retrospectively searched the medical records of all patients less than or equal to 18years old at a large children's hospital (May 2013 to September 2021). The inclusion criteria were (a) biopsy-proven diagnosis of LCH and (b) initial staging PET/CT and skeletal survey performed less than or equal to 1month apart. A blinded pediatric radiologist reviewed the skeletal surveys and another reviewed the PET/CTs in identifying LCH osseous lesions. Our study cohort consisted of 49 children with 86 LCH osseous lesions. In non-extremity locations, PET/CT identified 70/70 (100%) osseous lesions, while skeletal surveys detected 43/70 (61.4%) osseous lesions. In the extremities, PET/CT identified 13/16 (81.3%) osseous lesions, while skeletal surveys detected 15/16 (93.8%) osseous lesions. Skeletal surveys increased the detection rate of osseous lesions in the extremities, but added no diagnostic value to the detection of osseous lesions in non-extremity locations. Therefore, we propose to abbreviate the skeletal survey to include only extremity radiographs.

STAGE 0 HEPATIC SARCOIDOSIS WITH SUPERIMPOSED PRIMARY BILIARY CIRRHOSIS

STAGE 0 HEPATIC SARCOIDOSIS WITH SUPERIMPOSED PRIMARY BILIARY CIRRHOSIS

Thanatophoric dysplasia: a case report at Federal Medical Centre Yenagoa, Bayelsa state Nigeria

Thanatophoric dysplasia is a rare congenital severe skeletal disorder previously considered lethal but some survivals beyond the neonatal period have been reported due to extensive medical interventions. There have been a few studies on thanatophoric dysplasia in Africa and specifically in Nigeria hence this case report of an 8-day old female who was born with clinical features that were consistent with thanatophoric dysplasia creating awareness in this region. An eight-day old female term neonate who was seen in the special care baby unit with respiratory distress and limb abnormalities from birth. Two obstetric ultrasound scans had revealed a fetus with severe limb deformity. At presentation, she was in respiratory distress, with dysmorphic features, small chest wall with chest hypertelorism. The limbs were short having marks of amniotic bands with lymphoedema affecting both lower limbs. There were no palmar creases. Skeletal survey done revealed marked hypoplasia of the chest cavity, and widening of both proximal and distal epiphyses of all long bones showing telephone receiving appearance. Echocardiography and abdominal ultrasound scans were normal. It was documented that thanatophoric dysplasia was inherited in an autosomal dominant fashion however sporadic mutations do occur as seen in this patient who had no family history. Facility for genetic testing to analyse the fibroblast growth factor receptor (FGFR3) for typing and determining possible mutations was not available to confirm the diagnosis however, her clinical features and radiological findings were suggestive of thanotophoric dysplasia type 1.

Stones, Bones, and Groans with Cancerous Overtones - A Rare Case of Diffuse Large B Cell Lymphoma Presenting as Hypercalcemia

Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that can present in a variety of ways including fever, weight loss, weakness, and drenching night sweats. Uncommonly, hypercalcemia of malignancy can be associated with DLBCL through multiple mechanisms that include synthesis of parathyroid hormone related peptide (PTHrP) or elevated calcitriol levels. It is estimated that hypercalcemia in the setting of DLBCL is present in 18% of newly diagnosed cases. This report details a case of an 80-year-old man with history of chronic anemia and CKD stage 3b that presented with weakness, decreased oral intake, and self-reported weight loss. Initial labs showed a corrected calcium of 14.1 mg/dL and normal phosphorous and alkaline phosphatase levels. PTH was decreased at 4 pg/mL. Serum protein electrophoresis and skeletal survey were unremarkable. A continued anemia of 8.1 g/dL in the setting of hypercalcemia prompted further investigation with endoscopy and colonoscopy which showed a large malignant-appearing mass in the mid gastric body. Pathology identified the mass as DLBCL germinal center type. Labs taken after endoscopy reported elevated 1,25-dihydroxyvitamin D levels, consistent with vitamin-D induced hypercalcemia seen in DLBCL. This case report highlights an uncommon yet important presentation of DLBCL. It is imperative that a differential diagnosis for undifferentiated hypercalcemia in an older patient should include malignancies such as DLBCL and workup should include extrarenal causes of hypercalcemia such as PTHrP production and calcitriol levels.

Primary amyloidosis of conjunctiva.

A 64-year old male presented in ophthalmology OPD for follow up for refractive errors. He had been wearing bifocal lenses from last 1 year. On local examination, medial canthus of left eye showed a pale yellowish plaque. The rest of the ocular examination and contralateral eye were normal. Slit lamp examination showed a confluent fusiform papule (Figure 1A,B). Computed tomography (CT) scan of the orbit showed no abnormality. Surgical excision was done and tissue sent for histopathological examination showed deposition of a pink homogeneous material in the fibrocollagenous tissue beneath the conjunctival epithelium (Figure 1,C). Congo red stain followed by polarizing microscopy confirmed the pink material to be amyloid with apple green birefringence (Figure 1D,E). Immunohistochemistry (IHC) showed lambda light chain restriction. A diagnosis of conjunctival amyloidosis was made. The patient was then evaluated to rule out systemic amyloidosis or plasma cell dyscrasia. The patient was asymptomatic with no history of trauma, systemic illness, and family history was non-contributory. General and systemic examinations were unremarkable. Complete hemogram, urea, creatinine, liver function test, erythrocyte sedimentation rate, blood glucose, and serum calcium were within normal limits. No abnormality was detected on skeletal survey, electrocardiography, 2D-echocardiography, and ultrasonography of abdomen. Serum protein electrophoresis, serum immunofixation electrophoresis, serum free light chain assay, 24-h urine protein, and urine protein electrophoresis were non-contributory. Bone marrow showed mildly increased plasma cells without light chain restriction on immunohistochemistry. Finally, a diagnosis of primary conjunctival amyloidosis was made and the patient was asked to follow up. Conjunctival amyloidosis occurs secondary to local inflammation and primary form of the disease is very rare. In a previous series published on ocular amyloidosis, only two of 26 ocular cases collected over 30 years had conjunctival involvement. Identification of the disease is a daunting task owing to protean manifestations. Differentiating it from conjunctival inflammation and malignancies is essential. Evaluation for systemic causes is important as the treatment modalities are completely different. While localized form might just need observation or surgical debulking, systemic AL amyloidosis or myeloma would necessitate administration of specific chemotherapy. A long-term follow up is also necessary as recurrence is a known phenomenon and evolution into systemic disease is also a possibility. Concepts design, definition of intellectual content, Literature search, data analysis, manuscript preparation, and manuscript editing: Karuna Jha. Concepts design, definition of intellectual content, manuscript editing: Maitreyee Bhattacharyya. Dr Bhaskar Mitra, Consultant Pathologist, Tribedi and Roy Lab, Kolkata. The authors declare they have no conflicts of interest. The authors received no specific funding for this work. No research on human was performed on this study. Informed consent was taken from the patient. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Dedicated convolutional neural network for noise reduction in ultra-high-resolution photon-counting detector computed tomography

Objective. To develop a convolutional neural network (CNN) noise reduction technique for ultra-high-resolution photon-counting detector computed tomography (UHR-PCD-CT) that can be efficiently implemented using only clinically available reconstructed images. The developed technique was demonstrated for skeletal survey, lung screening, and head angiography (CTA). Approach. There were 39 participants enrolled in this study, each received a UHR-PCD and an energy integrating detector (EID) CT scan. The developed CNN noise reduction technique uses image-based noise insertion and UHR-PCD-CT images to train a U-Net via supervised learning. For each application, 13 patient scans were reconstructed using filtered back projection (FBP) and iterative reconstruction (IR) and allocated into training, validation, and testing datasets (9:1:3). The subtraction of FBP and IR images resulted in approximately noise-only images. The 5-slice average of IR produced a thick reference image. The CNN training input consisted of thick reference images with reinsertion of spatially decoupled noise-only images. The training target consisted of the corresponding thick reference images without noise insertion. Performance was evaluated based on difference images, line profiles, noise measurements, nonlinear perturbation assessment, and radiologist visual assessment. UHR-PCD-CT images were compared with EID images (clinical standard). Main results. Up to 89% noise reduction was achieved using the proposed CNN. Nonlinear perturbation assessment indicated reasonable retention of 1 mm radius and 1000 HU contrast signals (>80% for skeletal survey and head CTA, >50% for lung screening). A contour plot indicated reduced retention for small-radius and low contrast perturbations. Radiologists preferred CNN over IR for UHR-PCD-CT noise reduction. Additionally, UHR-PCD-CT with CNN was preferred over standard resolution EID-CT images. Significance. CT images reconstructed with very sharp kernels and/or thin sections suffer from increased image noise. Deep learning noise reduction can be used to offset noise level and increase utility of UHR-PCD-CT images.