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OBJECTIVES: To compare the diagnostic performance and radiological staging impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to 99 Tc whole-body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa). PATIENTS AND METHODS: A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as 'negative', 'equivocal', or 'definite' based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases). RESULTS: There were 667 patients included. The median (interquartile range) prostate-specific antigen level was 9.2 (6.2-16) ng/mL and 60% of patients were high risk according to a modified D'Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high-risk (P = 0.030) and low-risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUVmax ) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUVmax of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high-risk patients. The SUVmax of the primary tumour and metastases was associated with upstaging.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Estudos Prospectivos , Radioisótopos de Gálio , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologiaRESUMO
The fundamental basis of pregnancy and cancer is to determine the fate of the survival or the death of humanity. However, the development of fetuses and tumors share many similarities and differences, making them two sides of the same coin. This review presents an overview of the similarities and differences between pregnancy and cancer. In addition, we will also discuss the critical roles that Endoplasmic Reticulum Aminopeptidase (ERAP) 1 and 2 may play in the immune system, cell migration, and angiogenesis, all of which are essential for fetal and tumor development. Even though the comprehensive understanding of ERAP2 lags that of ERAP1 due to the lack of an animal model, recent studies have shown that both enzymes are associated with an increased risk of several diseases, including pregnancy disorder pre-eclampsia (PE), recurrent miscarriages, and cancer. The exact mechanisms in both pregnancy and cancer need to be elucidated. Therefore, a deeper understanding of ERAP's role in diseases can make it a potential therapeutic target for pregnancy complications and cancer and offer greater insight into its impact on the immune system.
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Neoplasias , Pré-Eclâmpsia , Complicações na Gravidez , Humanos , Gravidez , Feminino , Animais , Aminopeptidases , Retículo Endoplasmático , Antígenos de Histocompatibilidade MenorRESUMO
Knowledge of the fasting plasma glucose of healthy women may assist in the setting of treatment targets for women with hyperglycaemia in pregnancy (HIP). This study examines the pregnancy glucose tolerance test results of 3344 women without HIP collected over a three-year period. The median fasting plasma glucose was 4.4 mmol/L with an interquartile range of 4.2-4.6 mmol/L and a 5th to 95th centile of 3.8-4.9 mmol/L. As the diagnostic fasting glucose level for HIP is ≥5.1 mmol/L, these data support a treatment target of ≤5.0 mmol/L.
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Glicemia/metabolismo , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/terapia , GravidezRESUMO
BACKGROUND: The Australasian Diabetes in Pregnancy Society (ADIPS) has recently endorsed the World Health Organization (WHO) terminology and classification of hyperglycaemia in pregnancy. The prevalence is likely to increase, but no prospective data are available for a representative Australian population. AIMS: To determine the prevalence of hyperglycaemia in pregnancy (HIP) using results from both the public and private sectors in a population that has a similar ethnicity to the overall Australian population. MATERIAL AND METHODS: The results of all pregnancy oral glucose tolerance tests (POGTT) in the public sector and by a dominant private pathology provider in a major city have been prospectively collected for a three-year period and analysed using the ADIPS (WHO) criteria. RESULTS: The prevalence of hyperglycaemia in pregnancy (HIP) was 13.1% with diabetes mellitus in pregnancy (DIP) being 0.4% and gestational diabetes mellitus (GDM) being 12.7%. CONCLUSION: The new criteria will diagnose about one-third more women with GDM than the previous ADIPS criteria. This will have resource and health implications. Focussed local health economic data will be important.
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Diabetes Gestacional/epidemiologia , Hiperglicemia/epidemiologia , Gravidez em Diabéticas/epidemiologia , Setor Privado/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Cidades/epidemiologia , Feminino , Teste de Tolerância a Glucose , Humanos , New South Wales/epidemiologia , Gravidez , Prevalência , Estudos ProspectivosRESUMO
An appreciable level of isotope labelling is essential for future NMR structure elucidation of mammalian biomaterials, which are either poorly expressed, or unexpressable, using micro-organisms. We present a detailed protocol for high level (13)C enrichment even in slow turnover murine biomaterials (fur keratin), using a customized diet supplemented with commercial labelled algal hydrolysate and formulated as a gel to minimize wastage, which female mice consumed during pregnancy and lactation. This procedure produced approximately eightfold higher fur keratin labelling in pups, exposed in utero and throughout life to label, than in adults exposed for the same period, showing both the effectiveness, and necessity, of this approach.
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Ressonância Magnética Nuclear Biomolecular , Proteínas/química , Animais , Camundongos , Ressonância Magnética Nuclear Biomolecular/métodos , Especificidade de ÓrgãosRESUMO
When localised prostate cancer recurs after treatment, it occurs predictably in sites such as the prostatic bed, pelvic lymph nodes, spine, lung, and liver. Urethral metastasis of prostate cancer is exceedingly rare. We report a case of urethral recurrence of prostate cancer presenting as new lower urinary tract symptoms in an 82-year-old male 10 years after robotic radical prostatectomy with a very low PSA level of 0.05µg/L. This rare case highlights the need to maintain a degree of suspicion for prostate cancer recurrence in patients with a late onset of or changing lower urinary tract symptoms after radical prostatectomy.
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OBJECTIVE: To determine the diagnostic accuracy of Bone Scan at different PSA levels for detecting skeletal metastases in men with biochemical recurrence of prostate cancer. METHODS: We conducted a retrospective review of the statewide RIS-PACS to identify 251 men with biochemical recurrence who underwent both a Bone Scan and Ga68 PSMA PET/CT (within 2 months of each other) between September 2019 and December 2022 at a single institution. The Ga68 PSMA PET/CT report was considered to be the reference standard. RESULTS: The median age was 72 years (IQR 67-76) with a median PSA level of 1 ng/ml (IQR 0.25-2.8). Using Ga68 PSMA PET/CT as the reference standard, 68/251 patients (25%) were positive for osseus metastases. Overall sensitivity and specificity of Bone Scan was 51% (95% CI 40-64%) and 99% (95% CI 98-100%) respectively. Using PSA banding, a PSA threshold of 20 ng/ml provided the greatest discriminatory benefit with sensitivity of the Bone Scan below the threshold being 46% (95% CI 33-59%) and above the threshold being 89% (95% CI 68-100%). Specificity remained consistently high both below and above this threshold. CONCLUSION: Bone Scan provides greater diagnostic accuracy for detecting skeletal metastases in biochemical recurrence when the PSA level is above 20 ng/ml. This knowledge is valuable in optimising imaging algorithms in biochemical recurrence, particularly in regions where PSMA PET/CT is less readily available or affordable.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Radioisótopos de Gálio , Isótopos de Gálio , Oligopeptídeos , Ácido Edético , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologiaRESUMO
This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.
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Comportamento de Escolha/fisiologia , Dissonância Cognitiva , Modelos Psicológicos , Autoimagem , Conformidade Social , Adulto , China/etnologia , Comportamento do Consumidor , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
ABSTRACT: A 68-year-old woman was referred for an 18 F-FDG PET/CT for evaluation of arthralgia and raised inflammatory markers, which demonstrated intense FDG activity (SUV max , 25.5) at numerous periarticular and extra-articular sites including the cervical and lumbar interspinous bursae, lumbar facet joints, bilateral ischial tuberosities, and greater trochanters and the aorta consistent with active polymyalgia rheumatica.
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Arterite de Células Gigantes , Polimialgia Reumática , Feminino , Humanos , Idoso , Polimialgia Reumática/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodosRESUMO
ABSTRACT: A 69-year-old man with locally advanced prostate adenocarcinoma (Gleason score 9), who had completed hormone therapy and definitive radiotherapy, presented to hospital with abdominal pain and distension. A CT scan of the abdomen and pelvis revealed ascites and extensive peritoneal/omental nodules. Serum prostate-specific antigen was not raised (0.07 µg/L). 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT demonstrated PSMA-avid disease in the prostate and widespread PSMA-avid peritoneal/omental and liver metastases but with no PSMA-avid bony metastases. Peritoneal nodule biopsy confirmed metastatic prostate cancer.
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Neoplasias Peritoneais , Neoplasias da Próstata , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Isótopos de Gálio , Próstata/patologia , Neoplasias Peritoneais/diagnóstico por imagem , Radioisótopos de Gálio , Neoplasias da Próstata/patologia , Ácido EdéticoRESUMO
Prostate specific membrane antigen (PSMA) is expressed by hepatocellular carcinoma (HCC). PSMA PET/CT has potential as an imaging agent for the detection of HCC including early diagnosis and monitoring for recurrence following surgical resection. This study aims to compare PSMA PET to standard surveillance imaging in the detection of HCC. Patients with suspected or treated HCC were prospectively recruited from a tertiary hospital outpatient clinic. In addition to routine surveillance imaging as recommended by the multidisciplinary team, a PSMA PET/CT was performed. Imaging and clinical characteristics were compared over a follow-up period of up to 12 months. In a cohort of 19 patients with known HCC or suspected recurrent HCC, PSMA PET/CT had similar efficacy to MRI for the detection of HCC, with a sensitivity of 91% and a specificity of 70% and sensitivity of 87% and a specificity of 73% for PSMA PET/CT and MRI, respectively. PSMA PET/CT had a higher negative predictive value of 90%. In this relatively large single centre study, PSMA is shown to have promising equivalence in performance and its role should be further evaluated in multi-centre prospective trials.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias da Próstata , Humanos , Masculino , Carcinoma Hepatocelular/diagnóstico por imagem , Radioisótopos de Gálio , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Neoplasias da Próstata/patologiaRESUMO
A 60-year-old man with a background of resected clear cell renal cancer and resected colorectal adenocarcinoma presented with a pulmonary mass lesion in the left upper lobe which was avid on 18-F FDG PET/CT. Needle biopsy confirmed metastatic renal cell cancer, which was surgically excised with wedge resection. Follow-up imaging 6 months later demonstrated a second slowly enlarging subcentimeter nodule in the contralateral lung with increasing FDG avidity, suspicious of further small volume oligometastatic disease. Following surgical resection of the second pulmonary lesion, histopathological examination demonstrated nodular pulmonary amyloidosis and no evidence of malignancy.
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Pharmacists must be able to navigate prescription drug coverages to help providers and patients reduce out-of-pocket costs. Traditionally, curricula on drug insurance benefits rely on lectures and lack a practicum that offers students hands-on experience with determining formulary and cost-sharing information. An activity for pharmacy students to update a free public website that summarizes formularies and copayment requirements across major insurers was piloted. Pharmacy students were trained to locate online formularies and identify a drug's coverage tier, step therapy, prior authorization, and cost-sharing during a 6-week experiential rotation. Students checked formularies from six insurance plans for 250-plus drugs across 15 health conditions. Graduates were surveyed (74% response rate) about the activities' impact on their learning and ability to navigate drug benefits. Respondents rated the training as helpful in learning whether a drug was covered (100%), or required step therapy or prior authorization (100%). The majority of graduates reported being able to look up formulary coverage (90%), step therapy or prior authorization (90%), and copayment requirements (65%). Our innovative skills-based pilot activity was effective in teaching pharmacy students to navigate insurance formularies, which is essential for helping patients access medications.
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A 68-year-old gentleman was referred for 18F-FDG PET/CT for a pulmonary mass in the left upper lobe which demonstrated intensely FDG-avid confluent pulmonary consolidation in the left upper lobe (SUVmax 15.1). Histopathologic biopsy of the left upper lobe lung mass was consistent with inflammatory myofibroblastic tumor (IMT). The patient was started on steroid treatment in conjunction with antibiotics. Follow-up FDG PET/CT 3 weeks after commence of treatment showed remarkable response of the IMTs to therapy with much less avid FDG uptake (SUVmax 5.4) and marked improvement in the pulmonary consolidation. Nevertheless, the patient underwent left upper lobe lobectomy due to evidence of persistent cystic disease and malignant potential associated with IMTs. Final histopathology was consistent with IMT with no evidence of malignancy.
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ABSTRACT: A 73-year-old woman with metastatic breast cancer and known widespread skeletal metastases was referred for bone scintigraphy. Delayed images acquired at 2 and 5 hours postinjection of 30 mCi (1089 MBq) 99mTc-HDP demonstrated markedly reduced bony uptake, markedly increased renal activity, and significantly increased soft tissue accumulation. By contrast, appropriate skeletal uptake of 99mTc-HDP was seen in prior bone scans. The patient had been treated for iron deficiency anemia with an infusion of 1 g of iron polymaltose approximately 22 hours before injection of 99mTc-HDP. This phenomenon may be due to transient reduced bone resorption with increased FGF23 release secondary to IV iron supplementation.
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Neoplasias Ósseas , Neoplasias da Mama , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Feminino , Compostos Férricos , Humanos , Cintilografia , Tomografia Computadorizada por Raios XRESUMO
Fas-associated death domain (FADD) and caspase-8 are key signal transducers for death receptor-induced apoptosis, whereas cellular FLICE-inhibitory protein (cFLIP) antagonizes this process. Interestingly, FADD and caspase-8 also play a role in T cell development and T cell receptor (TCR)-mediated proliferative responses. To investigate the underlying mechanism, we generated cFLIP-deficient T cells by reconstituting Rag-/- blastocysts with cFLIP-deficient embryonic stem cells. These Rag chimeric mutant mice (rcFLIP-/-) had severely reduced numbers of T cells in the thymus, lymph nodes, and spleen, although mature T lymphocytes did develop. Similar to FADD- or caspase-8-deficient cells, rcFLIP-/- T cells were impaired in proliferation in response to TCR stimulation. Further investigation revealed that cFLIP is required for T cell survival, as well as T cell cycling in response to TCR stimulation. Interestingly, some signaling pathways from the TCR complex appeared competent, as CD3 plus CD28 cross-linking was capable of activating the ERK pathway in rcFLIP-/- T cells. We demonstrate an essential role for cFLIP in T cell function.
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Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Linfócitos T/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Caspase 8 , Caspases/metabolismo , Proliferação de Células , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína de Domínio de Morte Associada a Fas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Knockout , Receptores de Antígenos de Linfócitos T/metabolismoRESUMO
A 63-year-old lady with a background of ischemic heart disease was referred for 18F-FDG PET/CT for multiple lytic bone lesions which showed disseminated FDG avid lesions in the skeleton, nodal stations as well as spleen simulating advanced malignancy such as diffuse lymphomatous disease. A diagnosis of sarcoidosis was pathologically confirmed with bone biopsy. Following treatment, repeat PET/CT revealed significant regression of FDG avid lesions, however prominent uptake in the lateral ventricular wall was suspicious for active cardiac sarcoidosis, particularly given recurrent chest pain. This was confirmed on cardiac MRI and correlation with PET enabled discrimination between ischemic and non-ischemic fibrosis.
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Although primary cardiac tumours are extremely uncommon, secondary tumours or cardiac metastasis are not. We present a 68-year-old gentleman with squamous cell carcinoma of the right lower lobe with bony metastasis to the right clavicle who was treated with radiotherapy to the lung and clavicle as well as combination immunotherapy (Pembrolizumab) and chemotherapy (Carboplatin/Paclitaxel). Despite completing the above treatment regime, 18F-FDG PET/CT scan showed progression with two new sites of metastasis including a focus in the lateral wall of the right ventricle which correlate to a soft tissue density mass on CT as well as a FDG avid mass in the left masseter. Identification of cardiac lesions with 18F-FDG PET/CT maybe challenging with routine preparation due high physiological FDG uptake in the myocardium and significant variability, nevertheless, focal FDG uptake in the heart should be carefully assessed for the possibility of cardiac metastasis.
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ABSTRACT: A 66-year-old man was referred for a 68Ga-prostate-specific membrane antigen (PSMA) PET/CT scan for primary staging of Gleason 8 prostatic adenocarcinoma. The PET/CT images confirmed PSMA activity in the bilateral prostatic apex in keeping with the known malignancy. An intensely PSMA-avid focus was also noted in a nonenlarged right femoral lymph node with no evidence of PSMA-avid metastatic disease elsewhere. Subsequent core biopsy and histopathology confirmed a solitary metastatic focus of prostatic adenocarcinoma in a right femoral lymph node.