Soft Tissue Deposits Research Articles

Infected Tumoral Calcinosis Associated With Rheumatoid Arthritis.

Tumoral calcinosis (TC) is a syndrome of unknown etiology characterized by calcium salt deposition in soft tissues.1 A case of infected TC with rheumatoid arthritis (RA) is described.

7984 A Challenging Case Of Hyperphosphatemic Familial Tumoral Calcinosis

Abstract Disclosure: T.G. de Souza: None. T.J. Weber: None. Introduction: Hyperphosphatemic Familial Tumoral Calcinosis (hFTC) is a rare, autosomal recessive metabolic disorder characterized by elevated serum phosphate levels and the accumulation of calcium phosphate deposits in soft tissues. There are fewer that 150 genetically confirmed cases in the literature. There are no consensus guidelines; therapeutic approaches are guided by case reports or series. This case serves to heighten awareness of therapeutic strategies including global health considerations for the disabled adult with a rare bone disorder. Case: A 32-year-old African-American woman presented to establish care for hFTC, for which she takes ibuprofen for disabling bilateral hip pain. hFTC was diagnosed in early childhood and managed at a large children’s hospital. Therapeutic modalities relied on operative resection of skin lesions on eruption. She describes cosanguinous parentage, consignment to foster care as a child and homelessness as an adult. She has not had adult endocrine care for her hFTC. Her medical comorbidities include major depressive disorder, PTSD and suicide attempt. She reports one uncle with hFTC noting that his phenotype was not significantly disabling and apparent recession of his lesions with age. Her parents did not have symptoms of hFTC. Radiographically, she had amorphous calcium deposits over both hips (her primary sites of severe pain), upper back (site of painless spontaneous eruptions), and left elbow without pain or skin penetration, as well as hyperostosis of the ilium bilaterally. She noticed waxing and waning of her eruptions with her menstrual cycle, such that lesions worsen in the luteal phase. Megestrol acetate also induced new eruptions. Examination shows brown staining to all teeth with several missing teeth. She had a marked lower extremity limb length discrepancy with severe restriction of hip abduction. Blood chemistries were grossly normal, including renal function, calcium, uric acid and PTH. Serum phosphorous was elevated at 5.2 (2.3 - 4.5 mg/dL). CT showed bilateral nephrocalcinosis. We instituted treatment with a low phosphorous diet, sevelamer to reduce intestinal phosphate absorption and acetazolamide to increase urinary phosphate excretion. For her pain and functional disability, we recommended continued NSAIDs, physical therapy and social work consultation to facilitate continued access to care. Conclusions: This case uniquely describes hFTC symptom fluctuation with the menstrual cycle, worsening with increased progesterone, suggesting a possible role of gonadal hormones on FGF-23 biology. It also highlights the socioeconomic burdens that can accompany rare bone disease, which become more pronounced as the patient achieves adulthood. Successful transition of care from pediatric to adult endocrinologist, in addition to engaging multi-disciplinary support, is essential in optimizing life-long care in hFTC. Presentation: 6/1/2024

Malignant Soft Tissue Deposits in Advanced Cancer Larynx, a Prospective Study

Malignant Soft Tissue Deposits in Advanced Cancer Larynx, a Prospective Study

Clinicopathological Spectrum of Head and Neck Lesions By FNAC at a Tertiary Care Centre in Barpeta, Assam – A Retrospective Study

Background: Various neoplastic and non-neoplastic lesions arising from lymph nodes, salivary glands, thyroid gland, soft tissue and metastatic deposits comprises the wide spectrum of lesions in the head & neck region. The Foundation of Head and Neck Cancer (FHNC) helps in differentiating non-neoplastic lesions from neoplastic and further from benign and malignant lesions. The aim of this study was to evaluate the role and diagnostic accuracy of FNAC in diagnosis of palpable head and neck lesions. Materials and methods: A total of 360 cases were included in the study. Out of the 360 cases, 122 (33.89%) cases were sent for histopathological examination and the results were correlated histologically. Aspirations were done by using 10 ml syringe and 22/23-gauge needles. Smears were stained with May Grunwald Giemsa (MGG). Cytomorphological diagnosis was given. Results: Out of 360 patients of head and neck lesions studied, lymph node (40.56%) was the predominant site aspirated with reactive lymphoid hyperplasia being the commonest lesion. Soft tissue constitutes 31.11% cases followed by thyroid lesions with 19.72% cases, salivary gland 7.22% cases, and oral cavity 1.39% cases. FNAC was inconclusive in 4.17% cases. Conclusion: Head and neck lesions are common lesions located superficially that can be easily diagnosed on cytology. Although excisional biopsy is the gold standard for diagnosing head and neck malignant lesions, FNAC plays a vital role as a quick and inexpensive diagnostic procedure with high diagnostic accuracy. It distinguishes between inflammatory/infection and neoplastic lesions, avoiding needless procedures and expediting therapy. FNAC is a low-cost, accurate diagnostic method that may be used as a first-line examination.

Zinc Action in Vascular Calcification.

Although zinc's involvement in bone calcification is well-established, its role in vascular calcification, characterized by abnormal calcium and phosphorus deposition in soft tissues and a key aspect of various vascular diseases, including atherosclerosis, remains unclear. This review focuses on zinc's action in vascular smooth muscle cell (VSMC) calcification, including the vascular calcification mechanism. Accumulated research has indicated that zinc deficiency induces calcification in VSMCs and the aorta, primarily through apoptosis accompanied by a downregulation of smooth muscle cell markers. Moreover, zinc deficiency-induced vascular calcification operates independently of the action of alkaline phosphatase (ALP) activity, typically associated with osteogenic processes, but is partly regulated via inorganic phosphate transporter-1 (Pit-1). To date, research has shown that zinc regulates vascular calcification through a mechanism distinct from that of osteogenic calcification, providing insight into its dual effects on physiological and pathological calcification and thereby explaining the "zinc paradox," wherein zinc simultaneously increases osteoblastic calcification and decreases VSMC calcification.

#2214 Incidence, risk factors and outcome of calciphylaxis in Iceland

Abstract Background and Aims Calciphylaxis is a rare and serious medical condition that primarily affects patients with end-stage kidney disease (ESKD). The disorder is characterized by calcium deposition in blood vessels and soft tissues, resulting in skin ulceration and tissue necrosis. The aim of the study was to investigate the incidence, risk factors, and outcomes of calciphylaxis in Iceland. Method This was a retrospective case-control study that included individuals diagnosed with calciphylaxis in 1990-2022. Patients were identified by searching electronic medical records (EMR) for the ICD-10 diagnosis codes E83.5 and L94.2, SNOMED histology codes T01000-T03900 in combination with M55400, M55500 or M54000-M54200, documented sodium thiosulfate (STS) therapy, and by consultation with practicing nephrologists. Data on medical history, medication use, and survival were obtained from EMR. A control group of ESKD patients was matched (1:1) based on age, sex, and duration of dialysis. Total annual incidence was calculated per 1,000,000 population of Iceland each year, and for ESKD patients per 10,000 dialysis patients at the end of each year. Poisson regression was used to estimate changes in incidence. Groups were compared using non-parametric tests and survival estimated by Kaplan-Meier method and Cox regression. Results Twenty-one cases of calciphylaxis were identified, of which 18 (86%) had ESKD. The average incidence was 2/1,000,000/year. For ESKD patients, the median (interquartile range, IQR) age was 69 (66-75) years, and 50% were women. Three patients (17%) had not yet initiated dialysis at the time of diagnosis and the median duration of dialysis was 0.12 (IQR 0.0-2.8) years. The average incidence of calciphylaxis was 75 per 10,000 dialysis patients/year, increasing by 9.0% annually (Fig. 1). No significant differences between calciphylaxis cases and controls were observed for comorbid diseases or other risk factors. The median body mass index of cases was 29.5 (IQR 27.1-33.7) compared with 27.6 (IQR 24.3-30.6) kg/m2 in controls (p=0.20), and 50% of cases and 22% of controls (p=0.16) were on warfarin treatment at diagnosis. Fifteen patients received treatment with sodium thiosulfate (STS). Three of 6 patients received STS therapy before 2016 and all 12 patients after 2016. One-year mortality of ESKD patients with calciphylaxis was 44%. The median survival was 134 days in 1990-2016, increasing to 644 days after 2016. Survival difference between cases and controls was significant (p=0.04) by log rank test, while adjusted Cox regression did not show a statistically significant association between calciphylaxis and death (HR 2.0 (95% CI, 0.67-6.1)). Conclusion The incidence of calciphylaxis in Iceland seems to be increasing and is high compared to incidence rates reported in other countries. Survival, although poor, appears to have improved in recent years. The small sample size is a limitation and further research will require collaborative efforts to generate large patient samples.

Idiopathic Calcinosis Cutis of the left great toe-A case report

Calcinosis cutis, a rare benign disorder, involves systemic calcium deposition in soft tissues, often linked with autoimmune and renal disorders. Pathophysiology varies among its five main types: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Dystrophic calcification, the most common type, is associated with normal calcium and phosphorus levels and autoimmune diseases. Metastatic calcification, on the other hand, arises from abnormal serum calcium and phosphorus levels. Idiopathic calcification lacks underlying tissue damage or abnormal laboratory values. Iatrogenic calcification was triggered by calcium or phosphate-containing substances. Calciphylaxis involves vessel calcification and is linked to chronic renal failure and dialysis. A 19-year-old female presented with pain and swelling on her left great toe plantar aspect, diagnosed as unilateral idiopathic calcinosis cutis. A comprehensive diagnostic approach, including histopathological, radiological, and blood investigations, is crucial for effective management. The study aimed to highlight idiopathic cutaneous calcinosis, emphasizing its accurate diagnosis through clinical, pathological, and metabolic correlation. Surgical excision offers a complete cure for this rare condition, leading to an excellent prognosis.

Chemiluminescent and Photometric Analysis of Matrix Gla Protein from Patients with a Defect of Musculoskeletal System

Matrix Gla protein (MGP) is a circulating protein with a low molecular weight that acts as a natural inhibitor of calcification. It belongs to the group of vitamin K‑dependent proteins. For its proper function, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Its main function is the prevention of soft-tissue calcification. It requires vitamin K2 as a cofactor for gamma glutamyl carboxylase. Vitamin K insufficiency is manifested by cardiovascular diseases, insufficient mineralization of bone tissue and the formation of calcifying deposits in soft tissues. The aim of this study was to design methods for monitoring the levels of MGP and dp-uc MGP by using immunochemical detection and to apply them to the analysis of real samples for use in clinical laboratories. These markers could serve as potential markers of the severity of joint diseases, cardiovascular diseases and also as markers indicating the status of vitamin K in organism.

Cerebrotendinous Xanthomatosis: A Clinical Series Illustrating the Radiological Findings

Cerebrotendinous xanthomatosis is a rare autosomal recessive disorder that occurs due to defective bile acid biosynthesis, causing unusual cholesterol and cholestanol deposition in multiple soft tissues. It is manifested by various neurological and non-neurological symptoms. The characteristic imaging features and clinical symptoms can help to make an early diagnosis and induce timely treatment to prevent neurological sequelae. The authors present two adults with differing clinical symptoms, whose imaging provided pivotal cues in diagnosing cerebrotendinous xanthomatosis.

Physiological Calcium Phosphate Management in Two Biofluids

Management of calcium and phosphate in biofluids is key to maintaining physiological mineral homeostasis (i.e., appropriate mineralization of hard tissues and an absence of mineral deposition in soft tissues). This review describes and contrasts the ways vertebrates manage calcium phosphate in two biological fluids (breast milk and serum) and illustrates the benefits of mineral sequestration by proteins. In milk, phosphoprotein-sequestered calcium magnesium phosphates provide nutritional support, whereas in serum, protein-sequestered calcium phosphates control transport and delivery of calcium and phosphate to tissues for biological function or excretion. In addition, subsets of sequestered phosphates in serum have been identified as culprits underlying ectopic deposition of calcium phosphates and toxicity.

Carpal Tunnel Syndrome and Trigger Digit: An Early Symptom of Cardial Amyloidosis

Abstract Background Amyloidosis is a disease with misfolded protein deposits. The subform transthyretin amyloidosis (ATTR) presents with heart failure, atrial fibrillation and bundle branch block, often requiring pacing. Soft tissue deposits may occur, causing trigger digit (TD) and carpal tunnel syndrome (CTS). These may be an initial symptom of systemic amyloidosis with cardiac manifestation, they precede cardiac amyloidosis on average 5-9 years. Studies showed positivity of up to 22.5% for ATTR in tenosynovial biopsies in CTS-patients identified by a screening algorithm. ATTR is found in around 25% of autopsies at 80 years and older, with underestimated prevalence in the general population. Aims Early detection is crucial in treating systemic amyloidosis. Therefore, biopsies taken during carpal tunnel release (CTR) and trigger release (TR) can contribute significantly to its diagnosis. Methods Patients admitted in 2022 to our hospital were examined prospectively and biopsied if macroscopic intraoperative synovial hyperplasia was present. Histologic examination was done with Congo red staining and immunohistologic examination for ATTR. Patients tested positive for ATTR were offered a cardiologic follow-up. Results 118 patients (63 CTS, 55 TD) were included in the study, 40 (34%) underwent partial synovectomy. Of these, 3 patients (7.5%) were positive for ATTR. 1 patient had an unremarkable cardiologic examination, 1 patient declined, 1 patient is pending. Conclusions Early detection of amyloidosis by CTR and TR is a topic of increasing relevance. In our study, the positivity rate was lower than in others. However, there was different patient selection, e.g., according to macroscopic findings instead of a screening algorithm. The observation period is insufficient to record any cardiac results; a follow-up in 5-10 years would be appropriate. Current therapy for amyloidosis aims to delay the disease progress by preventing deposit formation, with no therapy degrading pre-existing deposits. Thus, early detection is crucial for disease outcome and justifies additional screening cost.

Abstract #1406447: A Case of Severe Hypercalcemia After Recovery from Rhabdomyolysis that was Refractory to Hemodialysis

Rhabdomyolysis (RBD) is severe skeletal muscle injury which often results in acute kidney injury (AKI) and significant electrolytes abnormalities. We herein describe a case of severe hypercalcemia that occurred during the recovery phase of RBD that was successfully treated with intravenous (IV) pamidronate. A 58-year-old male with history of cirrhosis, IgA nephropathy and chronic kidney disease presented with lower extremity weakness and was found to have AKI due to statin-induced RBD. Creatinine Kinase (CK) was > 30000 U/L [30-200], BUN 78 mg/dl [ 6-22], Creatinine 5.78 mg/dl [ 0.77-1.25], corrected Calcium (Ca) 7.0 mg/dl [8.6- 10.2], Ionized Ca 2.5 mg/dl [4.5- 5.3], Phosphorus 6.7 mg/dl [2.3-4.7], 25-OH Vitamin D 4.8 ng/ml [30 -80] and Parathyroid hormone (PTH) 333 ng/ml [8.7-77.1]. The patient received IV calcium gluconate, vitamin D supplementation and hemodialysis (HD) and was started on calcitriol 0.25 mg three times a week. He was discharged on calcitriol, calcium acetate and vitamin D with a corrected Ca of 9.1 mg/dl. One week later, the patient was readmitted with confusion and a corrected Ca of 15.3 mg/dl, phosphorus of 7 mg/dl, CK of 131 U/L, 25- OH vitamin D 10 ng/ml, PTH 11.4 ng/ml. Additional workup for hypercalcemia was unremarkable. His hypercalcemia persisted despite HD with low calcium baths, gentle IV hydration, and IV furosemide. Calcitonin 4 units/kg was initiated but his Ca remained 12.4mg/dl after 48 hours. IV pamidronate 30 mg was given and within 5 days, his Ca level was 9.4 mg/dl, reaching a nadir of 8.9 mg/dl. RBD is commonly associated with hypocalcemia in the acute phase. Hypercalcemia can also occur in the recovery phase, but few reports exist and the appropriate management has not been established. As in our case, overtreatment of hypocalcemia may exacerbate hypercalcemia. The pathophysiology of the hypercalcemia may be due to mobilization of Ca from injured muscles and soft tissue deposits. Secondary hyperparathyroidism can also contribute to a hypercalcemic response. Hypercalcemia due to RBD is usually self-limited but more severe cases can occur. Few have reported on the use of bisphosphonates for this condition. In our case, multiple treatments were not successful in lowering calcium. Despite concerns that bisphosphonates may not successfully lower calcium, since hypercalcemia was not mediated by bone turnover, calcium decreased after bisphosphonate therapy and no adverse effects were experienced. Therefore, bisphosphonate therapy can be considered in refractory post-rhabdomyolysis hypercalcemia.

A Case of Light Chain Deposition Disease Leading to Acute Liver Failure and Review of Literature

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver failure progressing to circulatory shock and multiorgan failure. After an extensive workup, a diagnosis of hepatic LCDD was determined. In conjunction with the hematology and oncology department, chemotherapy options were discussed, but given her poor prognosis, the family decided to pursue a palliative route. Though establishing a prompt diagnosis is important for any acute condition, the rarity of this condition, along with paucity of data, makes timely diagnosis and treatment challenging. The available literature shows variable rates of success with chemotherapy for systemic LCDD. Despite chemotherapeutic advances, liver failure in LCDD indicates a dismal prognosis, where further clinical trials are difficult owing to the low prevalence of the condition. In our article, we will also be reviewing previous case reports on this disease.

Utility of Gadolinium Use in the Imaging Follow-Up of Nonenhancing Primary Brain Neoplasms in Children.

Background and purpose Gadolinium-based contrast agents (GBCAs) have been administered clinically since 1988. They are remarkably well tolerated by children and result in dose-dependent tissue deposition, even in patients with normal renal function. No adverse effects of gadolinium deposition in patients with normal renal function have been established. Given the uncertain effects of gadolinium deposition, we sought to analyze gadolinium use in the imaging follow-up of nonenhancing primary brain neoplasms in children. Materials and methods This retrospective, institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study evaluated pediatric patients who received GBCA in the routine evaluation of brain neoplasms. This special subset included 30 patients (<18 years old) with initially nonenhancing primary intracranial neoplasms who received treatment and follow-up at our institution. Patient data included sex, age from diagnosis to most recent imaging follow-up, number of contrast-enhanced magnetic resonance imaging (MRI) follow-up exams, and histopathology from a biopsy or resection. Results The group had an expected variety of tumors, including low-grade astrocytomas, dysembryoplastic neuroepithelial tumors, oligodendrogliomas, and teratomas. Half of our patients had tumors of unknown histopathology that were not biopsied or resected. The median age at diagnosis was 8.9 years, the median of four follow-up MRIs per patient, and the median follow-up time of four years. Only one of the 30 patients developed an enhancing focus on follow-up MRI that remained stable and asymptomatic over two years and did not require surgical intervention. Conclusion Judicious use of GBCA in children, especially when numerous exams over many years are anticipated, is advised given the data regarding soft-tissue deposition. Preliminary results suggest that it may be feasible to omit GBCA from routine follow-ups of initially nonenhancing brain neoplasms.

Fetal Disseminated Malignant Rhabdoid Tumor.

Fetal Disseminated Malignant Rhabdoid Tumor.

Prevalence of Monosodium Urate (MSU) Deposits in Cadavers Detected by Dual-Energy Computed Tomography (DECT).

Background: Dual-energy computed tomography (DECT) allows direct visualization of monosodium urate (MSU) deposits in joints and soft tissues. Purpose: To describe the distribution of MSU deposits in cadavers using DECT in the head, body trunk, and feet. Materials and Methods: A total of 49 cadavers (41 embalmed and 8 fresh cadavers; 20 male, 29 female; mean age, 79.5 years; SD ± 11.3; range 52–95) of unknown clinical history underwent DECT to assess MSU deposits in the head, body trunk, and feet. Lens, thoracic aorta, and foot tendon dissections of fresh cadavers were used to verify MSU deposits by polarizing light microscopy. Results: 33/41 embalmed cadavers (80.5%) showed MSU deposits within the thoracic aorta. 11/41 cadavers (26.8%) showed MSU deposits within the metatarsophalangeal (MTP) joints and 46.3% of cadavers demonstrated MSU deposits within foot tendons, larger than and equal to 5 mm. No MSU deposits were detected in the cranium/intracerebral vessels, or the coronary arteries. Microscopy used as a gold standard could verify the presence of MSU deposits within the lens, thoracic aorta, or foot tendons in eight fresh cadavers. Conclusions: Microscopy confirmed the presence of MSU deposits in fresh cadavers within the lens, thoracic aorta, and foot tendons, whereas no MSU deposits could be detected in cranium/intracerebral vessels or coronary arteries. DECT may offer great potential as a screening tool to detect MSU deposits and measure the total uric acid burden in the body. The clinical impact of this cadaver study in terms of assessment of MSU burden should be further proven.

PSVIII-13 Utilization of a Mechanistic Model to Estimate the Mineral Deposition of Females and Entire Males Growing Pigs

Abstract Entire male (EM) production is increasing worldwide due to animal welfare regulations. The soft tissue growth and carcass composition of these animals were previously studied, but few data are available about mineral deposition. The objective in this study was to highlight, through modelling, potential differences in bone mineral deposition between female and EM, fed with identical diets. The data of 7 nutritional trials were used to simulate the mineral deposition in bones of EM and females. All diets were tested on both sexes and growth performances were reported. The trials started at about 32 kg of bodyweight and were divided into 2 phases: a growing phase (between 33 and 49 d, until 60 to 69 kg) and a finishing phase (between 47 and 61 d, until 110 to 125 kg). Protein and lipid depositions were calibrated following the InraPorc model principles. The minerals deposition in soft tissues and in bones were simulated according to a recent model predicting the utilization of minerals by growing pigs. The input data were the mean of each treatment, for each sex. The simulated bone mineral content (BMC) and bodyweight of the females and EM were comparable at the beginning of the trials. The BMC at the end of growing phase was less in EM than females (1,280 vs 1,298 g, P &amp;lt; 0.05), whereas bodyweight was equal. The BMC at the end of finishing phase tended to be less in EM than females (P = 0.10), and bodyweight was greater in EM than females (114 vs 116, P &amp;lt; 0.05).These results showed that during the growing phase, where the protein deposition increases quickly, the EM have less mineral in their bones than female. Therefore, with the same diet, these animals could be more sensitive to leg problems, which is reported in the field. These first results based on simulations showed that mineral requirements for EM are greater than females indicating that the mineral requirements must be adjusted according to the sex.

Angiogenesis versus Metabolic Imaging in Locally Advanced Breast Cancer Patients - A Comparative Study.

Purpose:The comparison of angiogenesis imaging (Ga-68-DOTA-Arginine-Glycine-Aspartic Acid [RGD]) positron emission tomography/computed tomography [PET/CT]) with metabolic imaging (F-18 fluorodeoxyglucose [FDG] PET/CT) in primary staging and response assessment to neoadjuvant chemotherapy (NACT) in locally advanced breast cancer (LABC) patients.Methods:In this prospective study, 85 female patients with LABC were subjected to two PET/CT studies (Ga-68-DOTA-RGD2 and F-18 FDG) within 1 week of each other. Thirty patients had repeat studies 4 weeks after completing eight cycles of NACT. Response assessment was done by RECIST 1.1 criteria.Results:Ga-68-DOTA-RGD2 and F-18 FDG uptake in the primary tumor were seen in all patients. Ipsilateral axillary and internal mammary lymph nodes were detected in 77 (90.5%) versus 80 (94.1%) and 22 (25.8%) versus 27 (31.7%) patients on Ga-68-DOTA-RGD2 and F-18 FDG scans, respectively. Ipsilateral supra-clavicular lymph nodes and skeletal lesions were noted in 17 (20%) versus 21 (24.7%) patients and 23 (27.0%) versus 24 (28.2%) patients on Ga-68-DOTA-RGD2 versus F-18 FDG studies, respectively. However, the Ga-68-DOTA-RGD2 did not show uptake in F-18 FDG avid liver lesions (LLs) in 10 patients, adrenal lesion in one patient, mediastinal lymph nodes in 2 patients, lung nodules, and pleural soft-tissue deposits, each in one patient. In response assessment, 23 and 25 patients had concordance with RECIST1.1 criteria on F-18 FDG and Ga-68-DOTA-RGD2 scans, respectively. However, there were discordant results in four patients on Ga-68-DOTA-RGD2 scan and two patients on F-18 FDG scans.Conclusion:Metabolic imaging is better in primary staging and chemotherapy response assessment than angiogenesis imaging in LABC patients. The latter may miss the metastatic soft-tissue deposits, adrenal, and LLs.

Live Imaging of Calciprotein Particle Clearance and Receptor Mediated Uptake: Role of Calciprotein Monomers.

BackgroundThe liver-derived plasma protein fetuin A is a systemic inhibitor of ectopic calcification. Fetuin-A stabilizes calcium phosphate mineral initially as ion clusters to form calciprotein monomers (CPM), and then as larger multimeric consolidations containing amorphous calcium phosphate (primary CPP, CPP 1) or more crystalline phases (secondary CPP, CPP 2). CPM and CPP mediate excess mineral stabilization, transport and clearance from circulation.MethodsWe injected i.v. synthetic fluorescent CPM and studied their clearance by live two-photon microscopy. We analyzed organ sections by fluorescence microscopy to assess CPM distribution. We studied cellular clearance and cytotoxicity by flow cytometry and live/dead staining, respectively, in cultured macrophages, liver sinusoidal endothelial cells (LSEC), and human proximal tubule epithelial HK-2 cells. Inflammasome activation was scored in macrophages. Fetuin A monomer and CPM charge were analyzed by ion exchange chromatography.ResultsLive mice cleared CPP in the liver as published previously. In contrast, CPM were filtered by kidney glomeruli into the Bowman space and the proximal tubules, suggesting tubular excretion of CPM-bound calcium phosphate and reabsorption of fetuin A. Fetuin-A monomer clearance was negligible in liver and low in kidney. Anion exchange chromatography revealed that fetuin A monomer was negatively charged, whereas CPM appeared neutral, suggesting electrochemical selectivity of CPM versus fetuin A. CPM were non-toxic in any of the investigated cell types, whereas CPP 1 were cytotoxic. Unlike CPP, CPM also did not activate the inflammasome.ConclusionsFetuin-A prevents calcium phosphate precipitation by forming CPM, which transform into CPP. Unlike CPP, CPM do not trigger inflammation. CPM are readily cleared in the kidneys, suggesting CPM as a physiological transporter of excess calcium and phosphate. Upon prolonged circulation, e.g., in chronic kidney disease, CPM will coalesce and form CPP, which cannot be cleared by the kidney, but will be endocytosed by liver sinusoidal endothelial cells and macrophages. Large amounts of CPP trigger inflammation. Chronic CPM and CPP clearance deficiency thus cause calcification by CPP deposition in blood vessels and soft tissues, as well as inflammation.

Dystrophic calcinosis cutis associated with systemic lupus erythematosus: a case report

Calcinosis cutis is a rare and potentially disabling condition characterized by calcium deposition in soft tissues. When associated with autoimmune connective tissue diseases, calcinosis cutis is classified as Dystrophic Calcinosis Cutis (DCC), being its occurrence in systemic lupus erythematosus (SLE) patients fairly uncommon. We report a case of DCC in a 49 years old woman with eleven years evolution SLE that presented with a two years history of multiple painful skin lesions, some of them ulcerated and exhibiting a chalky white-yellow floor, in both hands, forearms, thighs, buttocks, abdomen and left breast. The pelvic X-ray showed soft tissue calcifications and the skin biopsy confirmed the diagnosis of DCC. The patient was treated with diltiazem 240mg/day and a significant regression of the lesions and associated pain was observed. Dystrophic calcinosis cutis is often a painful and disrupting condition in which timely diagnosis and treatment may be quite challenging.