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In order to characterise soft tissue tumours, pathologists often utilise specialised additional tests, or may seek opinions from subspecialist pathologists due to rarity or complex morphology. Additionally, further review may be sought by subspecialist sarcoma pathologists, such as those at our tertiary referral centre in Sydney, Australia. The aim of this study was to examine the impact on diagnosis and management of this external review, following diagnosis at a specialised sarcoma unit. We collated the results of all additional external ancillary tests and specialist reviews over a 10-year period and characterised the impact on the preliminary diagnosis as 'confirmed', 'new' or 'no clear diagnosis'. We subsequently noted whether the additional findings resulted in a clinically significant change in management. Of the 136 cases sent away, 103 patients had their initial diagnosis confirmed, 29 patients received a new diagnosis and, for four patients, the diagnosis remained uncertain. Nine of the 29 patients receiving a new diagnosis had their management altered. This study demonstrated that within our specialised sarcoma unit, the majority of diagnoses provided by our specialist pathologists are confirmed on additional external testing and review, but external review does provide additional assurance and benefit to the patient.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/terapia , Sarcoma/patologia , Centros de Atenção Terciária , Patologistas , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologiaRESUMO
One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)-an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra-mass spectrometry (SWATH-MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2-2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.
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Injúria Renal Aguda/diagnóstico , Biomarcadores/metabolismo , Insuficiência Cardíaca/metabolismo , Proteômica/métodos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/urina , Humanos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Glicoproteínas da Membrana de Plaquetas/urina , Prognóstico , OvinosRESUMO
MYC over-expression by immunohistochemistry (IHC) is utilised in routine pathology practice as a surrogate marker for MYC amplification, which plays a key oncogenic role in post-irradiation and chronic lymphedema-associated angiosarcoma. We present the case of a 32-year old male, who presented with high-grade angiosarcoma arising in a background of metastatic testicular teratoma. IHC for MYC showed strong nuclear expression in the angiosarcoma cells prompting the consideration of post-irradiation-induced angiosarcoma but our patient did not undergo radiotherapy. Fluorescence in-situ hybridization (FISH) excluded MYC amplification and instead showed Chromosome 8 polysomy, which accounted for the strong MYC IHC expression present, not previously described in the context of germ cell tumours. The occurrence of MYC over-expression due to polysomy illustrates a novel clinical scenario (angiosarcoma arising as somatic malignancy) where strong MYC IHC expression can be found in the absence of underlying amplification or prior radiotherapy exposure.
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Hemangiossarcoma , Segunda Neoplasia Primária , Teratoma , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 8/metabolismo , Amplificação de Genes , Hemangiossarcoma/genética , Hemangiossarcoma/patologia , Humanos , Masculino , Segunda Neoplasia Primária/genética , Proteínas Proto-Oncogênicas c-myc/genética , Teratoma/genéticaRESUMO
Myoepithelioma-like tumours of the vulvar region (MELTVR) are a newly described group of spindle cell neoplasm. Morphologically, they consist of epithelioid to spindled cells in a myxoid to collagenous stroma and can resemble epithelioid sarcomas, myoepithelial carcinomas or extraskeletal myxoid chondrosarcomas. However, they have a distinct pattern of immunohistochemical staining characterised by positivity for EMA, ER, PR and negativity for cytokeratin, GFAP and S100. Nuclear staining for INI-1 is lost. In addition, they lack the characteristic gene arrangements of these other lesions. MELTVR can recur locally when incompletely excised, however, do not appear to metastasize. We report a case of a MELTVR in a 49-year-old woman arising in the right mons pubis.
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Mioepitelioma/patologia , Neoplasias Vulvares/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mioepitelioma/cirurgia , Neoplasias Vulvares/cirurgiaRESUMO
This paper contributes to research on health disparities among rural and urban residents by considering differences in the magnitude of genetic associations for physical health, mental health, and health behaviors across the two settings. Previous research has shown reduced genetic associations in rural compared to urban settings but none have utilized current genome-wide polygenic scores and none have focused on older adults. Using a sample of 14,994 adults from the 1992 to 2016 waves of the Health and Retirement Study our results suggest genetic associations for BMI (p<.018) and heart conditions (p < .023) are significantly reduced in rural compared to urban settings and we find weak evidence in support of this association for depression (p. < .065) and no evidence for smoking (p < 461). In sum, the weaker genetic associations in rural areas highlights the centrality of the social, economic, and built environment as a determinant of disparities.
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Aortitis is found in 2-12% of thoracic aortic aneurysm repair/replacement surgeries. Yet little is known about such patients' post-operative outcomes or the role of post-operative corticosteroids. The study was undertaken across three tertiary referral hospitals in Sydney, Australia. Prospectively collected data for all thoracic aortic repair/replacement patients between 2004 and 2018 was accessed from a national surgical registry and analysed. Histopathology records identified cases of inflammatory aortitis which were subclassified as clinically isolated aortitis (CIA), giant cell arteritis (GCA), Takayasu (TAK) or other aortitis. Between-group outcomes were compared utilising logistic and median regression analyses. Between 2004 and 2018, a total of 1119 thoracic aortic surgeries were performed of which 41 (3.7%) were inflammatory aortitis cases (66% CIA, 27% GCA, 5% TAK, 2% other). Eight out of 41 (20%) aortitis patients received post-operative corticosteroids. Compared to non-aortitis patients, the aortitis group was predominantly female (53.7% vs. 28.1%, p < 0.01), was older (mean 70 vs. 62 years, p < 0.01) and had higher prevalence of hypertension (82.9% vs. 67.1%, p = 0.03) and pre-operative immunosuppression (9.8% vs. 1.4%, p < 0.01). There was no difference (p > 0.05) between aortitis and non-aortitis groups for 30-day mortality (7.3% vs 6.5%), significant morbidity (14.6% vs. 22.4%), or infection (9.8% vs. 6.4%). Outcomes were similar for the non-corticosteroid-treated aortitis subgroup. Histologic evidence of inflammatory thoracic aortitis following surgery did not affect post-operative mortality or morbidity. Withholding corticosteroids did not adversely affect patient outcomes. These findings will assist rheumatologists and surgeons in the post-operative management of aortitis.
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Aortite , Arterite de Células Gigantes , Corticosteroides/uso terapêutico , Aorta Torácica/cirurgia , Aortite/epidemiologia , Aortite/cirurgia , Estudos de Coortes , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/epidemiologia , Arterite de Células Gigantes/cirurgia , HumanosRESUMO
We re-evaluate the findings of one of the most cited and disputed papers in gene-environment interaction (GxE) literature. In 2003, a paper was published in Science in which the authors demonstrated that the relationship between stress and depression is moderated by a polymorphism in the promoter region (5-HTTLPR) of the gene SLC6A4. Replication has been weak and led many to challenge the overall significance of GxE research. Here, we utilize data from Add Health, a large, nationally representative, and well-powered longitudinal study to re-examine the genetic determinants of stress sensitivity. We characterize environmental sensitivity using a genome-wide polygenic indicator rather than relying on one polymorphism in a single candidate gene. Our results provide support for the stress-diathesis perspective and validate the scientific contributions of the original paper.
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Depressão/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Estresse Psicológico/genética , Adolescente , Adulto , Criança , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND Acute decompensated heart failure (ADHF) is associated with deterioration in renal function-an important risk factor for poor outcomes. Whether ADHF results in permanent kidney damage/dysfunction is unknown. METHODS AND RESULTS We investigated for the first time the renal responses to the development of, and recovery from, ADHF using an ovine model. ADHF development induced pronounced hemodynamic changes, neurohormonal activation, and decline in renal function, including decreased urine, sodium and urea excretion, and creatinine clearance. Following ADHF recovery (25 days), creatinine clearance reductions persisted. Kidney biopsies taken during ADHF and following recovery showed widespread mesangial cell prominence, early mild acute tubular injury, and medullary/interstitial fibrosis. Renal transcriptomes identified altered expression of 270 genes following ADHF development and 631 genes following recovery. A total of 47 genes remained altered post-recovery. Pathway analysis suggested gene expression changes, driven by a network of inflammatory cytokines centered on IL-1ß (interleukin 1ß), lead to repression of reno-protective eNOS (endothelial nitric oxide synthase) signaling during ADHF development, and following recovery, activation of glomerulosclerosis and reno-protective pathways and repression of proinflammatory/fibrotic pathways. A total of 31 dysregulated genes encoding proteins detectable in urine, serum, and plasma identified potential candidate markers for kidney repair (including CNGA3 [cyclic nucleotide gated channel subunit alpha 3] and OIT3 [oncoprotein induced transcript 3]) or long-term renal impairment in ADHF (including ACTG2 [actin gamma 2, smooth muscle] and ANGPTL4 [angiopoietin like 4]). CONCLUSIONS In an ovine model, we provide the first direct evidence that an episode of ADHF leads to an immediate decline in kidney function that failed to fully resolve after ≈4 weeks and is associated with persistent functional/structural kidney injury. We identified molecular pathways underlying kidney injury and repair in ADHF and highlighted 31 novel candidate biomarkers for acute kidney injury in this setting.
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Injúria Renal Aguda , Insuficiência Cardíaca , Injúria Renal Aguda/genética , Animais , Biomarcadores , Creatinina , Insuficiência Cardíaca/genética , Rim/fisiologia , Ovinos , Carneiro Doméstico , TranscriptomaRESUMO
We use genome-wide data from the 1992-2016 Health and Retirement Study (n = 12,090) to characterize obesity among older adults as genetically or socially oriented. To illustrate the significance of this approach for social epidemiological research, we deem those with the lowest genetic risk for obesity to be socially-behaviorally obese and obesity among those with the highest polygenic risk is characterized as genetically oriented. We then examine the association between obesity and four indicators of cardiovascular health (type-2 diabetes, hypertension, heart problems, and stroke) among those with low, average, and high genetic risk. Our results show that the association between obesity and cardiovascular health is significantly higher for those with the lowest genetic risk (e.g., social-behavioral obesity). We also demonstrate important sex differences such that this association is particularly strong for heart problems among men and hypertension and stroke among women. Our results further demonstrate the centrality of the social and behavioral determinants of health by utilizing detailed information across the human genome and add to both social and genetic epidemiology literatures.
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Diabetes Mellitus Tipo 2 , Hipertensão , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Obesidade/epidemiologia , Obesidade/genética , Fatores de RiscoRESUMO
BACKGROUND: Lymphocytic myocarditis is an uncommon condition with a variety of clinical presentations. Isolated involvement of the right ventricle (RV) is very rare. We present a case of a young woman who developed right ventricular dysfunction and arrhythmias as a consequence of this condition, which appeared to be chronic at diagnosis. CASE SUMMARY: A 26-year-old lady was admitted to hospital following routine echocardiography, requested for screening of pulmonary hypertension in the context of known hypersensitivity pneumonitis. This echocardiogram demonstrated severe right ventricular dilatation and impairment. She was also experiencing atrial fibrillation and non-sustained, symptomatic episodes of ventricular tachycardia. Endomyocardial biopsy revealed lymphocytic myocarditis. She was managed with azathioprine and prednisone, as well as sotalol and apixaban for her atrial fibrillation, and has had no complications in the 12 months since discharge. DISCUSSION: Lymphocytic myocarditis isolated to the RV has only been reported in two previous cases, both of which were acute, dramatic presentations. This is the first report of a chronic example of this disease process. Due to her intercurrent immunosuppression, this patient may have been pre-disposed to the condition either by re-activation of a latent viral infection or partial treatment of a true autoimmune lymphocytic myocarditis.
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Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in rats by adenine or aristolochic acid models but without increasing serum creatinine. After prolonged recovery (three to six weeks), AKI was induced with a subnephrotoxic dose of cisplatin. Urinary levels of kidney injury molecule-1 (KIM-1), cytochrome C, monocyte chemotactic protein-1 (MCP-1), clusterin, and interleukin-18 increased during CKD induction, without an increase in serum creatinine. After AKI in adenine-induced CKD, serum creatinine increased more rapidly, while increased urinary KIM-1, clusterin, and MCP-1 were delayed and reduced. Increased serum creatinine and biomarker excretion were associated with diffuse tubulointerstitial injury in the outer stripe of outer medulla coupled with over 50% cortical damage. Following AKI in aristolochic acid-induced CKD, increased serum creatinine, urinary KIM-1, clusterin, MCP-1, cytochrome C, and interleukin-18 concentrations and excretion were greater at day 21 than day 42 and inversely correlated with cortical injury. Subclinical CKD modified functional and damage biomarker profiles in diametrically opposite ways. Functional biomarker profiles were more sensitive, while damage biomarker diagnostic thresholds and increases were diminished and delayed. Damage biomarker concentrations and excretion were inversely linked to the extent of prior cortical damage. Thus, thresholds for AKI biomarkers may need to be lower or sampling delayed in the known presence of CKD.
Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Rim/fisiopatologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Adenina/toxicidade , Animais , Ácidos Aristolóquicos/toxicidade , Biomarcadores/sangue , Moléculas de Adesão Celular/urina , Quimiocina CCL2/urina , Cisplatino/toxicidade , Clusterina/urina , Creatinina/sangue , Citocromos c/urina , Modelos Animais de Doenças , Humanos , Interleucina-18/urina , Rim/patologia , Testes de Função Renal , Osteopontina/urina , Ratos , Ratos Sprague-Dawley , Eliminação Renal , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologiaRESUMO
BACKGROUND/AIMS: Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. METHODS: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. RESULTS: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. CONCLUSIONS: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.
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Injúria Renal Aguda/diagnóstico , Cisplatino/uso terapêutico , Cistatina C/efeitos dos fármacos , Dexametasona/administração & dosagem , Idoso , Animais , Antineoplásicos/uso terapêutico , Creatinina/sangue , Cistatina C/sangue , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ratos Sprague-DawleyRESUMO
AIM: Retroperitoneal sarcomas (RPSs) are large, rare tumors. The role of core biopsy for retroperitoneal masses identified by preoperative imaging is unclear and we report the safety and accuracy of core biopsies at a specialized sarcoma unit in Sydney, Australia. METHODS: A retrospective analysis of a prospectively collected database was performed to identify the safety and accuracy of core biopsies in patients who were confirmed to have RPS. RESULTS: Twenty-two patients underwent biopsies with no recorded morbidity or tumor seeding. RPS was correctly identified in 82%. Median follow-up was 19 months. CONCLUSION: We demonstrate that core biopsy is safe and can identify RPSs.
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Biópsia com Agulha de Grande Calibre/métodos , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Adulto , Idoso , Austrália , Biópsia com Agulha de Grande Calibre/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SegurançaRESUMO
Juxtafacet cysts are an uncommon cause of radiculopathy. They occur most frequently in the lumbar region, and their distribution across the spine correlates with mobility. Haemorrhagic complications are rare and may occur in the absence of any provocation, although there is some association with anticoagulation and trauma. We present a case of acute radiculopathy due to an L5/S1 juxtafacet cyst with unprovoked haemorrhage which was found to extend into ligamentum flavum. The patient underwent uncomplicated microscope assisted decompression with excellent results. The demographics, presentation, aetiology, and management of juxtafacet cysts are discussed.
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Peribiliary cysts are cystic dilatations of the extramural glands of the intrahepatic biliary tree. This disorder is uncommon and is usually asymptomatic. However, it may cause extrinsic biliary compression and consequently, obstructive jaundice. This paper describes 2 such cases presenting with jaundice. The etiology, natural history, investigation findings and treatment of this disorder are also discussed.