[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients.

PURPOSE: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. METHODS: This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. RESULTS: ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. CONCLUSION: Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Cardiac [99mTc]Tc-hydroxydiphosphonate uptake on bone scintigraphy in patients with hereditary transthyretin amyloidosis: an early follow-up marker?

PURPOSE: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments. METHODS: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated. RESULTS: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer. CONCLUSION: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients.

Ultra-fast whole-body bone tomoscintigraphies achieved with a high-sensitivity 360° CZT camera and a dedicated deep-learning noise reduction algorithm.

This study aimed to determine whether the whole-body bone Single Photon Emission Computed Tomography (SPECT) recording times of around 10 min, routinely provided by a high-sensitivity 360° cadmium and zinc telluride (CZT) camera, can be further reduced by a deep-learning noise reduction (DLNR) algorithm. METHODS: DLNR was applied on whole-body images recorded after the injection of 545 ± 33 MBq of [99mTc]Tc-HDP in 19 patients (14 with bone metastasis) and reconstructed with 100%, 90%, 80%, 70%, 60%, 50%, 40%, and 30% of the original SPECT recording times. RESULTS: Irrespective of recording time, DLNR enhanced the contrast-to-noise ratios and slightly decreased the standardized uptake values of bone lesions. Except in one markedly obese patient, the quality of DLNR processed images remained good-to-excellent down to 60% of the recording time, corresponding to around 6 min SPECT-recording. CONCLUSION: Ultra-fast SPECT recordings of 6 min can be achieved when DLNR is applied on whole-body bone 360° CZT-SPECT.

EANM position paper on challenges and opportunities of full-ring 360° CZT bone imaging: it's time to let go of planar whole-body bone imaging.

The introduction of smaller footprint, more sensitive Cadmium-Zinc-Telluride (CZT)-based detectors with improved spatial and energy resolution has enabled the design of innovative full-ring 360° CZT SPECT/CT systems (e.g., VERITON® and StarGuide™). With this transformative technology now aiming to become mainstream in clinical practice, several critical questions need to be addressed. This EANM position paper provides practical recommendations on how to use these devices for routine bone SPECT/CT studies, facilitating the transition from traditional planar whole-body imaging and conventional SPECT/CT to these novel systems. In particular, initial guidance is provided on imaging acquisition and reporting workflows, image reconstruction, and CT acquisition parameters. Given the emerging nature of this technology, the available evidence base is still limited, and the proposed adaptations in workflows and scan protocols will likely evolve before being integrated into definitive guidelines. In the meantime, this EANM position paper serves as a comprehensive guide for integrating these advanced hybrid SPECT/CT imaging systems into clinical practice and outlining areas for further study.

Emerging Role of Scintigraphy Using Bone-Seeking Tracers for Diagnosis of Cardiac Amyloidosis: AJR Expert Panel Narrative Review.

Amyloidoses are a complex group of clinical diseases that result from progressive organ dysfunction due to extracellular protein misfolding and deposition. The two most common types of cardiac amyloidosis are transthyretin amyloidosis (ATTR) and light-chain (AL) amyloidosis. Diagnosis of ATTR cardiomyopathy (ATTR-CM) is challenging owing to its phenotypic similarity to other more common cardiac conditions, the perceived rarity of the disease, and unfamiliarity with its diagnostic algorithms; endomyocardial biopsy was historically required for diagnosis. However, myocardial scintigraphy using bone-seeking tracers has shown high accuracy for detection of ATTR-CM and has become a key noninvasive diagnostic test for the condition, receiving support from professional society guidelines and transforming prior diagnostic paradigms. This AJR Expert Panel Narrative Review describes the role of myocardial scintigraphy using bone-seeking tracers in the diagnosis of ATTR-CM. The article summarizes available tracers, acquisition techniques, interpretation and reporting considerations, diagnostic pitfalls, and gaps in the current literature. The critical need for monoclonal testing of patients with positive scintigraphy results to differentiate ATTR-CM from AL cardiac amyloidosis is highlighted. Recent updates in guideline recommendations that emphasize the importance of a qualitative visual assessment are also discussed.

Limited utility of routine bone scintigraphy in the staging of patients with hepatocellular carcinoma: A cross-sectional study.

INTRODUCTION AND OBJECTIVES: The most widely used staging system for hepatocellular carcinoma (HCC) is the Barcelona Liver Clinic Cancer (BCLC) system, which considers tumor burden, performance status, and liver function. Tumor burden is assessed with cross sectional imaging of the abdomen and chest, controversy surrounds the routine use of bone scintigraphy (BS) for detecting extrahepatic metastases. This study evaluated the role of BS in staging HCC in Mexican patients. PATIENTS AND METHODS: Retrospective cross-sectional study of all adults with HCC at a Mexican referral center from 2000 to 2018. Staging included abdominal computed tomography (CT) or magnetic resonance imaging, chest CT, and BS. The main outcome was the impact of BS on staging and/or therapy plans. RESULTS: Among 238 patients, 2 with fibrolamellar variant and 44 with incomplete data were excluded. Median age was 66 years, 84 % had cirrhosis, and the predominant etiology was hepatitis C virus (43 %). BCLC stages were distributed as follows: A (14 %), B (7 %), C (68 %), and D (11 %). Extrahepatic disease was present in 18 %; only 8 % patients had a positive BS. Among the positive cases, 4 were true positives, but they did not alter staging or therapy plans. CONCLUSIONS: Routine BS in HCC staging demonstrated low yield, with a notable rate of false positives. Considering the implications of extrahepatic disease, BS may be justified for liver transplant candidates outside conventional criteria. Our study highlights the limited role of BS in early-stage HCC and advocates for a more selective utilization.

Erdheim-Chester disease and nuclear medicine imaging. A case report and brief review.

Erdheim-Chester disease (ECD) is a rare clonal myeloid neoplasm typically affecting adults over 50 years old, with bone lesions in almost all patients. The prognosis is poor in most cases if left untreated. Clinical manifestations are not specific, which hinders early diagnosis. The disease has distinct radiological features. However, three-phase bone scintigraphy exhibits the most typical pattern of all imaging modalities, which is the prominent strikingly symmetrical radiotracer uptake in the distal ends of the femurs and proximal and distal ends of the tibiae, sparing the epiphyses. We report a case of a 54-year-old female patient, presenting with atypical persistent knee joint pain. After an MRI scan, she underwent a three-phase bone scan, revealing the characteristic pattern, thus indicating a possible ECD diagnosis, which was eventually confirmed in biopsy material. Novel aspects of the pathophysiology and treatment of the disease, as well as a differential diagnosis from the perspective of an MSK radiologist and nuclear medicine physician, are also discussed.

Large language model may assist diagnosis of SAPHO syndrome by bone scintigraphy.

OBJECTIVE: In this study, we employed a large language model to evaluate the diagnostic efficacy of radiology reports of bone scintigraphy in the context of identifying SAPHO syndrome, and further examined the potential of such a model to augment the diagnostic procedure. METHODS: Imaging data and clinical information of 151 patients (105/46 women/men, mean age: 53.5 years) who underwent bone scintigraphy for suspected Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) syndrome between January 2007 and December 2022 were retrospectively reviewed. ChatGPT-4.0 was used as the large language model. The diagnostic performance of the large language model was verified by comparing the cases judged to have SAPHO syndrome that fulfilled Kahn's classification criteria based on a combination of concise radiology reports and skin lesions such as palmoplantar pustulosis, with cases diagnosed with SAPHO syndrome by rheumatologists based on all clinical information. RESULTS: The diagnostic accuracy of a large language model for analysing bone scintigraphy radiology reports in conjunction with information about skin symptoms, such as palmoplantar pustulosis, achieved a sensitivity of 83.5%, specificity of 69.4%, and an overall accuracy of 76.8%. CONCLUSION: This research indicates the prospective value of extensive language models in scrutinizing radiology accounts from bone scintigraphy for the diagnosis of SAPHO syndrome.

The value of bone SPECT/CT in evaluation of foot and ankle arthrodesis and adjacent joint secondary osteoarthritis.

OBJECTIVE: To evaluate the value of SPECT/CT (single photon emission computed tomography/computed tomography) in foot and ankle arthrodesis and development of secondary osteoarthritis in the adjacent joints. MATERIALS AND METHODS: SPECT/CT of 140 joints in the foot and ankle (34 upper ankle (UA), 28 lower ankle (LA), 27 talonavicular (TN), 12 calcaneo-cuboidal (CC), and 39 other smaller joints after arthrodesis in 72 patients were evaluated retrospectively regarding fusion grade in CT (0 = no fusion, 1 = < 50% fusion, 2 = > 50% fusion, 3 = complete fusion) and radiotracer uptake (0 = no uptake, 1 = mild uptake, 2 = moderate uptake, 3 = high uptake) on SPECT/CT. Severity of osteoarthritis (1 = mild, 2 = moderate, 3 = severe) and radiotracer uptake grade in adjacent joints was also assessed. In 54 patients, clinical information about interventions in the follow-up was available. RESULTS: According to the SPECT/CT, arthrodesis was successful (grade 2 or 3 CT fusion and grade 0 or 1 uptake) in 73% (25/34) of UA joints, 71% (20/28) of LA joints, 67% (18/27) TN, 100% (12/12) CC joints, and 62% (24/39) of other smaller joints. In 12 joints, there were discrepant findings in SPECT/CT (fusion grade 2 and uptake grade 2 or 3 (n = 9); or, fusion grade 0 or 1 and uptake grade 1 (n = 3)). The fusion rate 6-12 months after arthrodesis was 42% (14/33), 59% (20/34) after 13-24 months, and 89% (65/73) after more than 24 months, respectively. Average radiotracer uptake in arthrodesis decreased with age: 6-12 months: 1.60, 12-24 months: 1.32, > 24 months: 0.38. There was a significant negative correlation between radiotracer uptake grade and CT fusion grade. Osteoarthritis was observed in 131 adjacent joints. During the post scan follow-up, additional arthrodeses were performed in 33 joints, of which 11 joints were re-arthrodesis and 22 were new arthrodeses in osteoarthritic adjacent joints. All these 11 joints with failed arthrodesis had grade 0 of CT fusion and grade 2 or 3 of radiotracer uptake. All 22 adjacent joints with osteoarthritis, which subsequently underwent arthrodesis, had grade 2 or 3 radiotracer uptake, and the primary arthrodesis joints were healed and fused in all these cases. CONCLUSION: Bone SPECT/CT is a valuable hybrid imaging tool in the evaluation of foot and ankle arthrodesis and gives additional useful information about the development of secondary osteoarthritis in the adjacent joints with higher value for the assessment of secondary osteoarthritis. A practical four-type classification ('Lucerne Criteria') combining metabolic and morphologic SPECT/CT information for evaluation of arthrodesis joints has been proposed.

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

BACKGROUND: With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP. METHODS: Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated. RESULTS: The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04). CONCLUSION: This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

SPECT/CT Scan: A New Diagnostic Tool in Pain Medicine.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the role of SPECT/CT in identifying facet joint arthropathy and the outcomes of interventions with SPECT/CT as an adjunct. RECENT FINDINGS: A positive finding of facet arthropathy on SPECT/CT is associated with a higher likelihood of a unilateral procedure and a significantly more effective intervention compared with those performed on patients with facet arthropathy diagnosed only by clinical and/or radiologic examination. Surgical treatment of SPECT/CT-positive findings appears to have a good effect; however, due to limitations in the available studies, no strong conclusion can be drawn. SPECT/CT has a good correlation identifying pain generators in chronic neck and back pain. SPECT/CT-targeted facet interventions demonstrate a higher success rate, but SPECT/CT is not recommended as a first-line diagnostic tool prior to diagnostic facet interventions. More robust studies are needed to confirm the higher success of surgical treatment for SPECT/CT-positive facet arthropathy.

Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

Assessment of clinical and radiological characteristics of Japanese patients with SAPHO syndrome.

OBJECTIVE: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. METHODS: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34, mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. RESULTS: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying anti-rheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. CONCLUSION: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. METHODS: The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. RESULTS: There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. CONCLUSIONS: A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

Head-To-Head Comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP Bone Scintigraphy for the Detection of Bone Metastases in Patients With Prostate Cancer: A Meta-Analysis.

BACKGROUND. Bone scintigraphy (BS) using 99mTc-labeled methylene diphospho-nate (99mTc-MDP) remains the recommended imaging modality for the detection of bone metastases in patients with prostate cancer (PCa). However, PET/CT using prostate-specific membrane antigen (PSMA) ligands is increasingly recognized as a means of evaluating disease extent in patients with PCa, including use as a possible stand-alone test in high-risk patients. OBJECTIVE. The purpose of this study is to compare the diagnostic performance of 68Ga-PSMA-11 PET/CT with that of 99mTc-MDP BS for the detection of bone metastases in patients with PCa. EVIDENCE ACQUISITION. The PubMed, Embase, and Cochrane Library databases were searched through October 2021 to identify studies reporting a head-to-head comparison of 68Ga-PSMA-11 PET/CT and 99mTc-MDP BS for the detection of bone metastases in patients with PCa. Only studies with a well-defined reference standard (including various combinations of imaging and/or clinical follow-up) were included. Pooled diagnostic performance was calculated using a bivariate random-effects model, and an AUC was derived for each test from hierarchic summary ROC analysis. The complementary roles of the two tests in identifying bone metastases in patients in whom one of the tests was negative were summarized. EVIDENCE SYNTHESIS. Six studies with 546 patients were included. Pooled sensitivity and specificity, respectively, were 98% (95% CI, 94-99%) and 97% (95% CI, 91-99%) for 68Ga-PSMA-11 PET/CT versus 83% (95% CI, 69-91%) and 68% (95% CI, 41-87%) for 99mTc-MDP BS. The AUC was 0.99 (95% CI, 0.96-1.00) for 68Ga-PSMA-11 PET/CT and 0.85 (95% CI, 0.81-0.87) for 99mTc-MDP BS. Among 408 patients from five included studies, 68Ga-PSMA-11 PET/CT correctly identified bone metastases in 43 of 193 patients (22.3%) with negative 99mTc-MDP BS results, whereas 99mTc-MDP BS correctly identified bone metastases in four of 210 patients (1.9%) with negative 68Ga-PSMA-11 PET/CT results. CONCLUSION. On a per-patient basis, the diagnostic performance of 68Ga-PSMA-11 PET/CT is superior to that of 99mTc-MDP BS for the detection of PCa bone metastases. Furthermore, 99mTc-MDP BS offers limited additional information in patients with negative 68Ga-PSMA-11 PET/CT results. CLINICAL IMPACT. According to current evidence, 99mTc-MDP BS is highly unlikely to be additive to 68Ga-PSMA-11 PET/CT in identifying bone metastases in patients with PCa.

Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive 99 mTc-Labeled Pyrophosphate Scintigraphy Findings.

BACKGROUND: The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue. CONCLUSIONS: Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet.

Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gαs/PKA and the Gαq/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gαq/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gαq/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gαq/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gαq/11 KO mice had similar bone morphology compared to WT, while CKD Gαq/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gαq/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gαq/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gαq/11/PKC KO further aggravates mineral bone disease.

Early Detection of Cardiac Amyloidosis in Transthyretin Mutation Carriers.

Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

Prognostic Value of 99mTc-HMDP Scintigraphy in Elderly Patients With Chronic Heart Failure.

BACKGROUND: This study evaluated the prevalence and prognostic significance of cardiac transthyretin amyloidosis (ATTR) diagnosed using 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy in an elderly heart failure population. METHODS: This retrospective study included 335 patients aged >70 years with heart failure and who underwent 99mTc-HMDP scintigraphy due to non-cardiac reasons in three imaging centres in Finland (Kymenlaakso Central Hospital, Jorvi Central Hospital, and Meilahti University Hospital). A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of ≥1.30 were considered positive for cardiac ATTR. The overall and cardiovascular mortality were obtained from the national statistical service (Statistics Finland). RESULTS: There were 234 deaths, of which 70 were classified as being due to cardiovascular causes during a median follow-up of 1 (1-3) year. Transthyretin amyloidosis was diagnosed in 22 patients (6.6%) using visual analysis and 17 patients using the H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs 80±5 yrs; p=0.002) and had higher N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels (1,451 [813-3,799] vs 6,192 [2,030-8,833] ng/L; p=0.02). Age, bone metastases, and glomerular filtration rate were independent predictors of overall mortality in multivariable analysis. Age, glomerular filtration rate, ≥grade 2 visual cardiac uptake, and H/CL ratio were independent predictors of cardiovascular mortality. CONCLUSIONS: Cardiac uptake suggestive of ATTR was found in 5% of elderly patients with chronic heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was independently associated with cardiovascular mortality.

Abnormal liver findings as the first manifestation in a patient with brucellosis : Case report.

In January 2019, a 30-year-old woman admitted to our inpatient department presented with undulating fever, pain in several joints, and significantly elevated liver enzymes and lactate dehydrogenase. After extended examination, infection with Brucella melitensis with liver, musculoskeletal, and pulmonary involvement was diagnosed and treated. Diagnosis was based on clinical examination, laboratory findings including seroconversion as a proof of immune response, magnetic resonance imaging, three-phase bone scintigraphy, and F­18 FDG-PET (F-18 Flourdeoxyglucose positron emission tomography) illustrating the bone involvement and its normalization upon treatment. After treatment the patient showed a remarkable improvement of clinical symptoms within a short period. The patient remained symptom free and polymerase chain reaction (PCR) testing for brucellosis was negative, even at the follow-up examination 12 months after the end of the antibiotic therapy. The family members were also examined due to the similar travel history, and by this, brucellosis was also diagnosed in her husband but not in her children.