Radioisotope Uptake Research Articles

Mechanical Ankle Joint Axis Point on a Hip-to-Calcaneus Long Leg View Correlates Significantly With SPECT/CT Activation in Symptomatic Asymmetric Ankle Osteoarthritis.

Asymmetric joint load is the main cause of development of ankle osteoarthritis (OA). Realignment surgery aims to transfer ankle joint load from the degenerative area toward the uninvolved area. Determination of the optimal shift is still challenging. When the degenerative area is correlated to the ankle joint mechanical axis establishing an optimal target angle for corrective surgery may become more feasible. The primary aim of our study was to investigate if the area of ankle joint activation on single-photon emission computed tomography and conventional computed tomography (SPECT/CT) imaging correlates with the mechanical ankle joint axis point (MAJAP). In this cross-sectional study, patients 18 years or older with symptomatic asymmetric ankle OA and a hip-to-calcaneus long leg view with SPECT/CT of the affected ankle were eligible for inclusion. Primary outcome was MAJAP divided into 3 alignment categories (medial shift, neutral, lateral shift). SPECT/CT activation was determined in 8 different areas of the ankle joint. A Spearman rho correlation coefficient was calculated to investigate the relationship between the alignment categories and SPECT/CT activation in the 8 areas. Forty-nine patients (mean age 58.8 [SD 10.0] years) with 52 ankles with moderate to severe asymmetric OA were included. A significantly (Spearman rho -0.379 [P = .006] and Spearman rho -0.279 [P = .045]) higher proportion of ankles with radioisotope uptake in the anteromedial ankle joint areas (zones 1 and 5) was seen in the medial shift category. A significantly (Spearman rho .312 (P = .025)) higher proportion of ankles with radioisotope uptake in the anterolateral ankle joint area (zone 8) was seen in the lateral shift category. We found in this patient group that the area of SPECT/CT uptake in asymmetric ankle OA was associated to MAJAP measured on hip-to-calcaneus weightbearing views, although the strength of the correlation is weak to moderate. Consequently, nonweightbearing metabolic SPECT/CT radiotracer uptake has the potential to help determine the area to unload in ankle joint-preserving alignment surgery.

A Rare Case of Retroperitoneal Schwannoma in an Adult Male

Objective. This study aims to illustrate a rare case of retroperitoneal schwannoma by presenting the clinical, imaging, and histological parameters. Case Report. A 36-year-old patient visited the outpatient clinic because of back pain experienced over the previous two months. There were no complaints regarding the nervous system or urinary system. Thorough imaging evaluation, including magnetic resonance for the lumbar spine, abdominal computed tomography, and positron emission tomography was conducted. An encapsulated mass was found in the retroperitoneal area, positioned in front of the O4 vertebra and in close proximity to the left psoas muscle, the left common iliac artery, and the left ureter. The lesion exhibited FDG radioisotope uptake, and a CT-guided biopsy confirmed a benign peripheral nerve tumor. The patient underwent laparotomy surgery, where the tumor was removed. The histological investigation, along with immunohistochemistry, confirmed the presence of a retroperitoneal schwannoma. Conclusion. Schwannoma is a rare type of retroperitoneal tumor, with nonspecific clinical and radiological characteristics that make diagnosis difficult. Surgical resection is the primary treatment for symptomatic patients, with a favorable prognosis. Long-term follow-up is advised to reduce the chance of late recurrence.

PROSTHETIC GRAFT INFECTION: WHEN ECHOCARDIOGRAPHY IS NOT ENOUGH!

Abstract A 68–year–old Caucasian male, post–Bentall procedure with a bioprosthetic valve following extensive aortic dissection involving the ascending aorta and aortic arch, presented to the Emergency Department with persistent fever for over a month. During his hospitalization, he experienced ventricular fibrillation in the setting of hypokalemia, successfully managed with Advanced Cardiovascular Life Support (ACLS) and DC shock, leading to the restoration of sinus rhythm. Subsequently, he was admitted to the Cardiovascular Intensive Care Unite. Blood tests revealed neutrophilic leukocytosis with elevated inflammatory markers, anemia, and a troponin curve consistent with myocardial injury in the context of sepsis and anemia. Echocardiography demonstrated a left ventricle of normal dimensions with globally depressed function (EF 45%), attributed to apical akinesia. The prosthetic valve was functioning normally, and there were no signs of endocarditic vegetations or pericardial involvement. A transesophageal echocardiogram confirmed the absence of vegetations. Given echocardiographic signs of myocardial ischemia, coronary angiography was performed, revealing a coronary circulation free from significant stenosis. Cultural exams showed positivity for Enterococcus faecalis. A PET–CT revealed the presence of radioisotope uptake around the vascular prosthesis situated in the aortic arch. An Infectious Disease specialist recommended antibiotic therapy with Piperacillin/Tazobactam and Teicoplanin. At the one–month follow–up, the patient remained asymptomatic, free from new febrile episodes. The follow–up echocardiogram indicated improved global systolic function, and inflammatory markers remained consistently negative. Repeat blood cultures were negative. This case illustrates a suspected endocarditis on a prosthetic valve where both transthoraci and transesophageal echocardiography yielded negative results. The use of PET–CT, on the other hand, revealed the presence of vascular graft infection, proving to be a valuable method in this clinical setting.

Sensibilidad de la respuesta simpática cutánea y de la gammagrafía en el diagnóstico del síndrome dolor regional complejo

ObjectiveTo evaluate the sensitivity of sympathetic skin response (SSR) and compare it with scintigraphy in patients with complex regional pain syndrome diagnosed according to the Budapest criteria. Material and methodsTwenty-two patients with complex regional pain syndrome who attended the Rehabilitation and Physical Medicine Department between January-2018 and May-2022 have been prospectively evaluated. The scintigraphy was considered positive if in the 1st-2nd phase slight asymmetric and diffuse uptake was observed, or when in the 3rd phase marked periarticular radioisotope uptake was observed. SSR was abnormal if: a) no response after 20 stimuli; b) lack of habituation with permanence of the stimuli greater than 67.2%. ResultsAge 55.4±8.57 years. Complex regional pain syndrome was more frequent in women (90.9%), more common in upper limbs (68.2%) than lower limbs (31.8%). In SSR, we have observed normal response (<67.2%) in 2 patients (11.1%), lack of SSR in 2 patients (11.1%) and lack of habituation (>67.2%) in 14 patients (77.8%). In total, 16 patients presented abnormal or absent responses (88.8%). The diagnostic sensitivity of scintigraphy is similar to that of SSR (89.5% vs 88.8%), with no statistical difference (P=.6721). ConclusionScintigraphy has shown similar sensitivity to SSR, although the simplicity, security, low cost, non-ionizing and non-invasiveness of the latter technique suggest that it could be more cost-effective. The lack of habituation and the absence of response could identify response patterns and localize the involvement in the afferent, central, efferent or post-ganglionic pathways.

Bioaccumulation of zinc by Portunus pelagicus: Nuclear application techniques that use radiotracer 65Zn to study influence of concentration of Zn in seawater

Zinc (Zn) is an essential trace metal, but also a potential toxicant to aquatic organisms. Zinc is one of the toxicants from various industrial and domestic activities whose waste is directly discharged into water. One of the marine organisms used as an indicator of pollution is the blue swimming crab (Portunus pelagicus). Bioaccumulation studies of Zn in Portunus pelagicus from Jakarta Bay were conducted in a radiotracer laboratory. Laboratory experiments were done to study the uptake and release of 65Zn radioisotope in Portunus pelagicus. The experiments conducted were biota collection, acclimatization, bioaccumulation, and elimination. This study was to determine the relationship between the amount of 65Zn released into the aquatic environment and its effect on Zn bioaccumulation ability and radiation dose received by Portunus pelagicus. Biokinetics parameters, such as concentration factors CF, uptake rate constant ku, elimination rate constant ke, and concentration factor steady state (CFss) were investigated. The results showed that an increase in concentration would decrease the rate of absorption and rate of elimination, and that the concentration factor CF values ​​varied from 7.82 - 60.62 ml.g-1 in Portunus pelagicus. The concentration factor at steady-state Zn was 25.55-59.47 ml.g–1, which is influenced by the concentration after 6 days of exposure. The depuration rate was observed to be high, with a value of retention 34.33 - 78.88 % of 65Zn absorbed by Portunus pelagicus, which was absent 7 days after exposure. Highlights Laboratory experiments lasting 14 days showed that Portunus pelagicus has the ability to accumulate the heavy metal zinc (Zn) from the environment and release it back into the water The highest bioaccumulation kinetics of zinc (Zn) metal in Portunus pelagicus during the 7-day experiment occurred at a contaminant concentration of 0.5 ppm with an absorption constant (ku) value of 0.7838 d-1 and a release constant value (ke) of 0.0892 d-1 Portunus pelagicus concentration factor (CF) has a moderate value and the smallest uptake constant (ku) and elimination constant (ke) value compared to other biota

Modifications in cellular viability, DNA damage and stress responses inflicted in cancer cells by copper-64 ions.

Due to combined therapeutical emissions, a high linear energy transfer Auger-electrons with the longer ranged β- particles, 64Cu-based radiopharmaceuticals raise particular theragnostic interest in cancer, by joined therapeutic and real-time PET imaging properties. The in vitro study aimed to investigate the biological and molecular background of 64CuCl2 therapy by analyzing the damages and stress responses inflicted in various human normal and tumor cell lines. Colon (HT29 and HCT116) and prostate carcinoma (DU145) cell lines, as well as human normal BJ fibroblasts, were treated up to 72 h with 2-40 MBq/mL 64CuCl2. Radioisotope uptake and retention were assessed, and cell viability/death, DNA damage, oxidative stress, and the expression of 84 stress genes were investigated at various time points after [64Cu]CuCl2 addition. All the investigated cells incorporated 64Cu ions similarly, independent of their tumoral or normal status, but their fate after exposure to [64Cu]CuCl2 was cell-dependent. The most striking cytotoxic effects of the radioisotope were registered in colon carcinoma HCT116 cells, for which a substantial decrease in the number of metabolically active cells, and an increased DNA damage and oxidative stress were registered. The stress gene expression study highlighted the activation of both death and repair mechanisms in these cells, related to extrinsic apoptosis, necrosis/necroptosis or autophagy, and cell cycle arrest, nucleotide excision repair, antioxidant, and hypoxic responses, respectively. The in vitro study indicated that 40 MBq/mL [64Cu]CuCl2 delivers a therapeutic effect in human colon carcinoma, but its use is limited by harmful, yet lower effects on normal fibroblasts. The exposure of tumor cells to 20 MBq/mL [64Cu]CuCl2, might be used for a softer approach aiming for a lower radiotoxicity in normal fibroblasts as compared to tumor cells. This radioactive concentration was able to induce a persistent decrease in the number of metabolically active cells, accompanied by DNA damage and oxidative stress, associated with significant changes in stress gene expression in HCT116 colon cancer cells.

Congenital hypothyroidism in Northern Ireland: 40years' experience of national screening programme.

The incidence of congenital hypothyroidism (CHT) has progressively increased in several regions around the world but has yet to be evaluated in Northern Ireland (NI). CHT screening programme was introduced in NI in 1980 and has had a relatively unchanged protocol since its inception. The purpose of the study was to evaluate the incidence of CHT in NI from 1981 to 2020 and to explore possible contributing factors to any changes seen over the 40-year period. This was a retrospective database review of children diagnosed with CHT in NI between 1981 and 2020. Data was collected from the patients' medical (paper and electronic) records, including epidemiological, clinical, laboratory, and radiological features as well as outcomes at 3 years. Of 800,404 new-borns who were screened for CHT in NI between January 1981 and March 2020, 471 were diagnosed with CHT. There was a steady and significant increase in incidence of CHT over time with an incidence of 26 cases per 100,000 livebirths in 1981 versus71 cases per 100,000 in 2019 (p < .001). Of these 471, 77 new-borns (16%) were born preterm. The incidence of CHT was observed twice as much in female compared to male new-borns. Diagnostic imaging including radioisotope uptake and thyroid ultrasound scans were performed in 143 cases (30%). Of these, 101 (70%) cases had thyroid dysgenesis and 42 (30%) cases had thyroid dyshormonogenesis. There were 293 (62%) of 471 patients had confirmed permanent CHT, and 90 patients (19%) had transient CHT. Over that period at least 95% of the population were recorded as having United Kingdom/Ireland as country of birth. Our findings demonstrate a nearly tripling of the CHT incidence observed over the last 40 years. This is against a background of a relatively stable population demographics. Future research should focus on the underlying cause(s) of this condition which may include changing environmental exposures in utero.

Malabsorption of Zinc in Rats with Acetic Acid-Induced Enteritis and Colitis

Acute intestinal inflammation was established in rats by intraluminal administration of acetic acid into loops of distal ileum, proximal jejunum or ascending colon. The study included two control groups of intact (untreated) rats and sham-operated (saline-treated) rats for each intestinal segment. A third group of rats received acetic acid. Histological evaluation demonstrated that acetic acid treatment induced a mild inflammatory response. Two days after treatment, zinc absorption was measured using ligated 10-cm loops of each segment in which 65Zn was injected intraluminally. 65Zn absorption by the ileum, jejunum and colon was markedly reduced in those rats in which inflammation was induced by acetic acid. The liver showed the highest uptake of radioisotope, but the relative tissue distribution generally followed the amount of absorption. The surgical procedure itself seemed to reduce zinc absorption. No changes in [3H]leucine absorption were observed between sham-operated and acetic acid-treated controls. There was no significant serosal-->luminal secretion of intramuscularly injected 65Zn in any of the studied segments. Therefore, based upon the data obtained, we conclude that acetic acid-induced intestinal inflammation reduces absorption of zinc by the small and large intestine, and that a surgical procedure (laparotomy) also reduces zinc absorption. The mechanism of this inflammation is such that malabsorption shows some specificity.

Successful Treatment of Congenital Hyperinsulinism Due to KJNJ11 Gene Mutation with Long-Acting Release Octreotide: A Case Report from the Arab Region

AbstractCongenital hyperinsulinism is a rare hereditary condition that is caused by various gene mutations related to the function of the pancreatic β-cells. It is characterized by dysregulation of insulin secretion leading to profound and recurrent hypoglycemia. Its clinical presentation, histology, response to treatment, and underlying genetic defects are variable making it a heterogeneous condition. Pancreatectomy is indicated in diazoxide un-responsive cases. However, surgical treatment is associated with the possibility of persistent hypoglycemia and iatrogenic diabetes. We report a 3 months old girl who presented with hyperinsulinemic hypoglycemia. She was born to consanguineous parents and had a history of four neonatal deaths in siblings. Whole exome sequencing detected a KCNJ11 variant c.350_352del p.(Phe117del) in a homozygous state. Pancreatic scan (positron emission tomography/computed tomography) showed a diffusely increased radioisotope uptake in the head and tail of the pancreas. She was resistant to diazoxide and nifedipine and was shifted to octreotide treatment through multiple daily subcutaneous injections initially. Treatment was changed to monthly depot injection of octreotide that resulted in euglycemia. She kept a normal rate of growth, insulin-like growth factor-1, and liver function. This case is an example of an alternative effective medical therapy that avoids major surgical intervention and prevents long-term complication of recurrent hypoglycemia and iatrogenic diabetes resulting after surgery.

PS-B11-6: ENDOTHELIAL GHRELIN RECEPTOR INCREASE WHITE FAT WEIGHT THROUGH ACTIVATION OF MTOR-PPARGAMMA PATHWAY

Ghrelin secretion from the stomach acts on peripheral tissues to cause weight gain and fat accumulation in white adipose tissue (WAT). The role of endothelial growth hormone secretagogue-receptor (GHSR) in lipid accumulation was evaluated by restoring the expression of GHSR only in the endothelial cells of GHSR-deficient mice using the Cre-LoxP system (GHSR-EC). Radioisotope (RI) -labeled H-triolein was orally administered to evaluate lipid uptake in WAT. GHSR-deficient mice had reduced RI uptake in WAT compared to control mice, and GHSR-EC mice recovered the reduced RI uptake in GHSR-deficient mice. Furthermore, the body weight and WAT weight of GHSR-deficient mice after high-fat diet loading were significantly decreased compared with control mice, but increased in GHSR-EC mice. In vitro studies, ghrelin stimulation increased the uptake of free fatty acids by GHSR-mediated activation of the mTOR pathway and increased expression of PPARgamma. From these results, ghrelin takes up lipids via endothelial GHSR and contributes to fat accumulation in white adipose tissue.

Gastrointestinal Bleeding in a Child: Is It a Meckel Diverticulum?

A 2-year-9-month-old boy with multiple episodes of melena and hematochezia with unclear cause was admitted to our hospital. Laboratory tests showed iron deficiency anemia (hemoglobin of 5 g/dL) and positive fecal occult blood test. Single-operator double-balloon enteroscopy (DBE) through the anal route was performed and revealed multiple patchy mucosal eminence consisted of ectopic gastric pit and loss of villi observed by electronic stain in the distal jejunum, approximately 2 m from the ileocecal valve. The bowel cavity was deformed like a maze in the distal jejunum. There are several mucosal bridging structures and focal stricture, making it difficult to determine the direction of the lumen. Two irregular deep ulcers were found near the stricture (A [a–f] and Video 1). Emission computer tomography Tc99m pertechnetate scan showed multiple areas of radioisotope uptake in the middle and lower abdomen. At laparotomy, a 46-cm-long cyst was noted on the mesentery aspect that protruded alongside from the distal jejunum (B [a–c]). Resection of 58 cm of the jejunum was performed including the cyst. Pathology showed a duplication cyst located on the mesenteric aspect with ectopic gastric mucosa (C). The postoperative diagnosis was a duplication cyst of the jejunum. The patient was discharged 14 days after surgery and remained symptom-free thereafter. Intestinal duplication cysts are rare congenital malformations that can appear anywhere in the gastrointestinal tract. The preoperative diagnosis of a duplication cyst is difficult and can be easily misdiagnosed as Meckel diverticulum. Duplication cysts usually locate on the mesenteric aspect as in our case, in contrast to Meckel diverticulum that localizes on the antimesenteric aspect. In our case, the deformed intestine was found approximately 2 m from the ileocecal valve, which was not common in Meckel diverticulum. To the best of our knowledge, this is the first reported tubular type of jejunal duplication cyst case with an DBE video. DBE can be a useful tool for the diagnosis of intestinal duplication in young children. Watch the Video, Supplementary Digital Content 1, https://links.lww.com/AJG/C853. (Informed consent was obtained from the patient to publish these images.)

99m Technetium-pyrophosphate bone scan: A potential biomarker for the burden of transthyretin amyloidosis in skeletal muscle: A preliminary study.

Transthyretin amyloidosis (ATTR) proteins can infiltrate skeletal muscle and infrequently cause a myopathy. 99m Technetium-pyrophosphate (99m Tc-PYP) is a validated biomarker for cardiac involvement in variant and wild-type ATTR (ATTRv and ATTRwt, respectively). The aim of this study was to test the hypothesis that 99m Tc-PYP is a biomarker for muscle burden of ATTR. Radioisotope uptake in the deltoid muscles of patients with ATTR was compared to uptake in control subjects without amyloidosis in a retrospective study. 99m Tc-PYP scans were evaluated in 11 patients with ATTR (7 ATTRv, 4 ATTRwt) and 14 control subjects. Mean count (MC) values were measured in circular regions of interest (ROIs) 2.5-3.8cm2 in area. Tracer uptake was quantified in the heart, contralateral chest (CC), and deltoid muscles. Tracer uptake was significantly higher over the deltoids and heart but not the CC, in patients with ATTR than in control subjects. MC values were 120.1± 43.7 (mean ± SD) in ATTR patients and 78.9± 20.4 in control subjects over the heart (p= 0.005), 73.3± 21.0 and 63.5± 14.4 over CC (p= 0.09), and 37.0± 11.7 and 26.0± 7.1 averaged over both deltoid muscles (p= 0.014). 99m Tc-PYP is a potential biomarker for ATTR amyloid burden in skeletal muscle.

Cherenkov light emission in molecular radiation therapy of the thyroid and its application to dosimetry.

Numerical experiments based on Monte Carlo simulations and clinical CT data are performed to investigate the spatial and spectral characteristics of Cherenkov light emission and the relationship between Cherenkov light intensity and deposited dose in molecular radiotherapy of hyperthyroidism and papillary thyroid carcinoma. It is found that Cherenkov light is emitted mostly in the treatment volume, the spatial distribution of Cherenkov light at the surface of the patient presents high-value regions at locations that depend on the symmetry and location of the treatment volume, and the surface light in the near-infrared spectral region originates from the treatment site. The effect of inter-patient variability in the tissue optical parameters and radioisotope uptake on the linear relationship between the dose absorbed by the treatment volume and Cherenkov light intensity at the surface of the patient is investigated, and measurements of surface light intensity for which this effect is minimal are identified. The use of Cherenkov light measurements at the patient surface for molecular radiation therapy dosimetry is also addressed.

The prevalence and significance of nonuniform thyroid radio-isotope uptake in patients with Graves' disease.

ObjectiveTo evaluate the prevalence and clinical significance of nonuniform technetium (99mTc) uptake among patients with Graves’ disease (GD).Design, Patients and MeasurementsPatients with GD, referred between July 2005 and March 2018, had Tc99‐ uptake scans and TSH‐receptor antibody (TRAb) measured before antithyroid drug (ATD) therapy. Risk of relapse after ATD cessation was monitored until June 2021 and compared between GD patients based on uptake patterns.ResultsOf the 276 GD patients (mean age, 49.8 years; 84% female), 25 (9.0%) had nonuniform Tc99 uptake. At diagnosis, individuals with nonuniform uptake were older (mean age of 61.8 vs. 48.5 years, p < .001), had lower mean thyroid hormone levels (free thyroxine: 36.3 vs. 45.4 pmol/L, p = .04 and free triiodothyronine: 10.0 vs. 17.8 pmol/L, p < .001) and median TRAb levels (4.2 vs. 6.6 U/L, p = .04) compared with those with a uniform uptake. Older age was a significant predictor for the presence of nonuniform uptake in GD patients; odds ratio (95% confidence intervals) of 1.07 (1.03 – 1.10). The risk of relapse was similar in both groups after a median (IQR) follow‐up of 41 (13–74) months after ATD cessation (56.0% vs. 46.3%, respectively); hazard ratio (95% confidence intervals) of 1.74 (0.96–3.15).ConclusionsNonuniform radio‐isotope uptake is seen in 1 in 11 patients with GD which could be misdiagnosed as toxic multinodular goitre if TRAb levels are not measured. Treatment of GD patients with nonuniform radio‐isotope uptake with ATD therapy as first‐line appears to be equally effective as compared with those with uniform uptake. TRAb testing should be the main diagnostic test for patients with suspected GD with radio‐labelled uptake scans being reserved for those who are TRAb negative.

Comparative Study Between Radioisotope Uptake and Fluorescence Intensity of Indocyanine Green for Sentinel Lymph Node Biopsy in Breast Cancer

Recently, several breast surgeons have reported a new method for sentinel lymph node biopsy (SLNB) by using indocyanine green (ICG) with infrared camera. This study aimed to determine whether the lymph nodes (LNs) with ICG uptake are true SLNs and to assess the reliability of using only ICG for SLNB. Data were prospectively collected between April and September 2021. All palpable LNs were fat-trimmed and ordered from high to low signal of the gamma detector. The degree of radioisotope uptake and brightness of ICG staining of the axillary LNs detected with a fluorescent camera were compared and associated factors were analyzed. Discordance was defined as sentinel LNs (SLNs) showing a single uptake of radioisotope or fluorescence of ICG only, or when the orders of uptake and intensity degree were different between the 2 materials. A total of 79 SLNBs were performed on 78 patients with breast cancer. The breast cancer was classified as cTis-2N0-1. The discordance rate was 14/79 (17.7%) overall and 45/270 (16.7%) of the total retrieved axillary LNs. The first SLNs showed the lowest discordance rate of 6.3%, whereas the second and third SLNs showed higher discordance rates of 27.6% and 60.0%, respectively. There were no associated clinicopathologic factors that affected the discordance between uptake of radioisotope and fluorescence intensity of ICG. The use of ICG alone for SLNB may be insufficient because of the high discordance rates between radioisotopes and ICG uptake. However, the first SLN could be cautiously regarded as a true SLN.

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

Whole-body magnetic resonance imaging vs. clinical evaluation of enthesitis in patients with spondyloarthritis

A case of “asymmetrical” Graves’ disease with lateral radioisotope uptake

A case of “asymmetrical” Graves’ disease with lateral radioisotope uptake

Unusual presentation of lumbar chordoma on bone scintigraphy in a young patient

Chordoma is a rare bone cancer which arises from undifferentiated notochordal remnants in the axial skeleton. It generally has slow-growing and locally aggressive behavior. This tumor is usually diagnosed by CT and MRI modalities and the role of SPECT/CT is still debated. It shows reduced or normal uptake of radioisotope on bone scanning and increased tracer uptake is infrequently reported. Here we present a 33-year-old man with complaint of low back pain and numbness of his right leg. The whole body bone scan showed relatively uniform radiotracer activity throughout the skeleton. A focal increased uptake in the second lumbar vertebra was noted on SPECT/CT images. SPECT/CT also demonstrated multiple lytic lesions in lumbar vertebrae. The lesions were proven to be chordoma on biopsy. Lumbar chordoma could be one of the differential diagnoses for lytic lesions of the vertebrae which show absent or minimal tracer uptake on bone scintigraphy and SPECT/CT imaging. Our case was unusual as the patient was very young for chordoma diagnosis and bone scan showed increased uptake adjacent to the involved vertebral lesion detected by SPECT/CT.

Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head.

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.

Abstract 16069: Molecular Dynamics Simulations Reveal the Functional Impact of Pathogenic Variants in the LDL Receptor LA 4-6 Repeats

Introduction: Functional annotation of rare variants is key to the implementation of genomic medicine. We used molecular dynamics (MD) simulations to assess functional consequences of putative pathogenic variants (PVs) in the low-density lipoprotein receptor gene ( LDLR ). LDLR has a multidomain structure with seven LA repeats and local interactions between these repeats influence ligand binding. However, binding and recycling of the receptor-ligand complex require global changes in conformation. Using MD, we investigated the effects of PVs on long-range dynamics and LDL binding. Methods: An LA 4-6 repeat structure was created from a crystal structure of the extracellular domain (PDB: 1N7D). Structures were solvated with a water box containing TIP3P water molecules and simulated using the AMBER software package with the ff14SB forcefield. The wild type (WT) structure was first relaxed using MD; and subsequently PVs D245Y, F181Y and F181G were modeled. Dynamics were simulated for approximately one microsecond. Values for LDL binding for each PV were obtained from a prior study which used a radioisotope uptake assay. Results: WT domains demonstrated a stable conformation based on root mean square deviation. PVs disrupted the normal distribution in all domains significantly (p &lt; 0.0001), broadening it and introducing multiple peaks. Projection along the top principal components (PCs) showed global destabilization with all PVs. The variant with the greatest impact on LDL binding, F181G, adopted a distinct alternate conformation. Comparison between PV and WT subspaces from PCA correlated with LDL binding (R 2 = 0.99, exponential regression). Structural analysis revealed that the LA5 calcium cage is involved in inter-domain salt bridges, which are disrupted in simulations of PVs. Conclusion: MD simulation of LA4-6 repeats in LDLR suggests PVs alter long-range conformational dynamics, and that such dynamics correlate with LDL binding. The impact of PVs on conformational dynamics and binding may be through disruption of interdomain salt bridges that are mediated by the acidic calcium cage. This study demonstrates the potential utility of MD simulations to functionally characterize LDLR variants.