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Sepsis is a major health care burden with significant contribution to morbidity, mortality, and hospital resource utilization. Monocyte Distribution Width (MDW), the novel hematological biomarker, was clinically implemented in our laboratory for early detection of sepsis (ESId) in 2019. When COVID-19 pandemic hit in 2020, we noticed some similarities of the laboratory data of the COVID patients with patients previously diagnosed with sepsis. The aim of this study was to evaluate the value of the hematological data including MDW in predicting COVID disease severity and outcome. A retrospective study was conducted on 130 COVID-infected patients who presented at our hospital during March and April 2020. Collected data included clinical, laboratory, and radiological findings. This study demonstrates a unique pattern of three hematological biomarkers that predicted severity and outcome in COVID patients at their initial presentation in the Emergency Room (ER): higher absolute neutrophil count (ANC), lower absolute lymphocyte count (ALC), and higher MDW.
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Biomarcadores , COVID-19 , Leucócitos , Sepse , Humanos , Biomarcadores/sangue , COVID-19/sangue , COVID-19/diagnóstico , Pandemias , Gravidade do Paciente , Valor Preditivo dos Testes , Estudos Retrospectivos , Sepse/sangue , Sepse/diagnóstico , Leucócitos/patologiaRESUMO
BACKGROUND: The glycated hemoglobin (A1c) test is not recommended for sickle cell disease (SCD) patients. We examine ordering patterns of diabetes-related tests for SCD patients to explore misutilization of tests among this underserved population. METHODS: We used de-identified electronic health record (EHR) data in the Cerner Health Facts™ (HF) data warehouse to evaluate the frequency of A1c and fructosamine tests during 2010 to 2016, for 37,151 SCD patients from 393 healthcare facilities across the United States. After excluding facilities with no A1c data, we defined three groups of facilities based on the prevalence of SCD patients with A1c test(s): adherent facilities (no SCD patients with A1c test(s)), minor non-adherent facilities, major non-adherent facilities. RESULTS: We determined that 11% of SCD patients (3927 patients) treated at 393 facilities in the US received orders for at least one A1c test. Of the 3927 SCD patients with an A1c test, only 89 patients (2.3%) received an order for a fructosamine test. At the minor non-adherent facilities, 5% of the SCD patients received an A1c test while 58% of the SCD patients at the least adherent facilities had at least one A1c test. Overall, the percent of A1c tests ordered for SCD patients between 2010 and 2016 remained similar. CONCLUSIONS: Inappropriate A1c test orders among a sickle cell population is a significant quality gap. Interventions to advance adoption of professional recommendations that advocate for alternate tests, such as fructosamine, can guide clinicians in test selection to reduce this quality gap are discussed. The informatics strategy used in this work can inform other largescale analyses of lab test utilization using de-identified EHR data.
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Anemia Falciforme , Diabetes Mellitus , Anemia Falciforme/diagnóstico , Registros Eletrônicos de Saúde , Frutosamina , Hemoglobinas Glicadas , Humanos , Estados UnidosRESUMO
Recent parechovirus A3 (PeV-A3) outbreaks in Australia suggest lower population immunity compared with regions that have endemic PeV-A3 circulation. A serosurvey among populations in the Netherlands, the United States, and Australia before and after the 2013 Australia outbreak showed high PeV-A3 neutralizing antibody prevalence across all regions and time periods, indicating widespread circulation.
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Anticorpos Antivirais/sangue , Surtos de Doenças , Parechovirus/imunologia , Infecções por Picornaviridae/epidemiologia , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/sangue , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Infecções por Picornaviridae/virologia , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Sonic hedgehog pathway is highly activated in pancreatic cancer stem cells (CSC) which play crucial roles in cancer initiation, progression and metastasis. However, the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics is not well understood. The objectives of this study were to examine the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics. Sanguinarine inhibited cell proliferation and colony formation and induced apoptosis through oxidative damage. Sanguinarine inhibited self-renewal capacity of pancreatic CSCs isolated from human and KrasG12D mice. Furthermore, sanguinarine suppressed epithelial-mesenchymal transition (EMT) by up-regulating E-cadherin and inhibiting N-cadherin. Significant decrease in expression level of Snail, Slug and Zeb1 corroborated the suppression of EMT in sanguinarine treated pancreatic CSCS. The ability of sanguinarine to inhibit pluripotency maintaining factors and CSC markers suggest that sanguinarine can be an effective agent for inhibiting pancreatic cancer growth and development by targeting CSCs. Furthermore, sanguinarine inhibited Shh-Gli pathway leading to modulation of Gli target genes in pancreatic CSCs. Chromatin immunoprecipitation assay demonstrated that Nanog directly binds to promoters of Cdk2, Cdk6, FGF4, c-Myc and Oct4, and sanguinarine inhibits the binding of Nanog with these genes, suggesting the direct involvement of Nanog in cell cycle, pluripotency and self-renewal. To further investigate the role of Shh-Gli-Nanog pathway, we regulated Shh signaling either by Shh protein or Nanog overexpression. Enforced activation of Shh or overexpression of Nanog counteracted the inhibitory effects of sanguinarine on pancreatic CSC proliferation, suggesting the actions of sanguinarine are mediated, at least in part, through Shh-Gli-Nanog pathway. Our studies suggest that sanguinarine can be used for the treatment and/or prevention of pancreatic cancer by targeting CSCs.
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Benzofenantridinas/farmacologia , Isoquinolinas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Camundongos , Proteína Homeobox Nanog/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
BACKGROUND: Fetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental origin. Information, however, on the role of specific proangiogenic and antiangiogenic mechanisms operating at the placental level remains limited. Elucidation of these placenta-specific angiogenic mechanisms will not only extend our understanding of the causal pathway for restricted fetal growth but may also lead to the development of biomarkers that may allow early recognition of FGR. OBJECTIVE: We sought to test the hypothesis that fetoplacental angiogenic gene expression is altered in pregnancies complicated with FGR and umbilical artery Doppler AEDF. STUDY DESIGN: Placental samples were collected from FGR pregnancies complicated with umbilical artery Doppler AEDF (study group, n = 7), and from uncomplicated pregnancies (control group, n = 7), all delivered by cesarean during the last trimester of pregnancy. Angiogenic oligonucleotide microarray analysis was performed and was corroborated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The Student t test with Bonferroni correction was used with P < .05 considered statistically significant. Independent groups t test was used to analyze the immunostain intensity scores with a P < .05 considered statistically significant. RESULTS: Our microarray results showed that among several differentially expressed angiogenic genes in the growth-restricted group, only the down-regulation of neuropilin (NRP)-1 was most significant (P < .0007). Quantitative real-time polymerase chain reaction confirmed a significantly lower NRP-1 gene expression in the FGR group than in the control group (mean ± SD (Ë)cycle threshold: 0.624 ± 0.55 and 1.325 ± 0.84, respectively, P = .04). Western blot validated significantly lower NRP-1 protein expression in the FGR group than in the control group (mean ± SD NRP-1/ß-actin ratio: 0.13 ± 0.04 and 0.34 ± 0.05, respectively, P < .001). Finally, immunohistochemistry of placental villi further corroborated a significantly decreased expression of NRP-1 in the FGR group (P = .006). CONCLUSION: The study demonstrated significant down-regulation of placental NRP-1 expression in FGR pregnancies complicated with AEDF in umbilical artery. As NRP-1 is known to promote sprouting angiogenesis, its down-regulation may be involved in the deficient vascular branching observed in FGR placentas suggesting the presence of an antiangiogenic state. Further studies may elucidate such a causal role and may lead to the development of novel diagnostic and therapeutic tools.
Assuntos
Retardo do Crescimento Fetal/genética , Neovascularização Fisiológica/genética , Neuropilina-1/genética , Placenta/metabolismo , Circulação Placentária , RNA Mensageiro/metabolismo , Artérias Umbilicais/diagnóstico por imagem , Adulto , Western Blotting , Estudos de Casos e Controles , Estudos de Coortes , Diástole , Regulação para Baixo , Feminino , Retardo do Crescimento Fetal/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Neuropilina-1/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Placenta/irrigação sanguínea , Gravidez , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Artérias Umbilicais/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES). METHODS: A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II. Either captopril, an Ang I converting enzyme inhibitor, or losartan, an Ang II type 1 receptor blocker, was injected 1 hour after FE by triolein injection. After euthanasia at 48 hours, histopathologic evaluation was used to compare the drug-treated animals with control animals that received only triolein. RESULTS: Histology of the lungs of rats treated only with triolein revealed severe, diffuse pathology. Alveolar septa showed severe, diffuse inflammation. Bronchial lumina showed severe mucosal epithelial loss. The media of the pulmonary small arteries and arterioles was thicker, and the lumen patency was reduced 60% to 70%. Trichrome staining confirmed the abundant presence of collagen in the media and adventitia, as well as collagen infiltrating the bronchial musculature. Both captopril and losartan treatments reduced the inflammatory, vasoconstrictor, and profibrotic effects present at 48 hours (p<0.001). With treatment, the vascular lumen remained patent, and the fat droplets were reduced in size and number. There was a reduction in the number of infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils, along with a significant decrease in hemorrhage and collagen deposition (p<0.001). Pathologic changes in bronchial epithelium were also diminished. CONCLUSIONS: The results suggest that the use of drugs that act on the renin-Ang system might provide an effective and targeted therapy for fat embolism syndrome.
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Captopril/farmacologia , Embolia Gordurosa/tratamento farmacológico , Losartan/farmacologia , Pulmão/patologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Embolia Gordurosa/patologia , Pulmão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
Aggressive digital papillary adenocarcinoma (ADPA) is a rare tumor that is considered to arise from eccrine sweat glands of the skin. It occurs predominantly in men with a mean age in the sixth decade. It shows a strong tendency for local recurrence and has the potential to metastasize to distant sites. Prompt diagnosis and regular follow-up are important to ensure the best possible outcome. We discuss a case of recurrent ADPA associated with subsequent squamous cell carcinoma (SCC) in different contralateral digits in a 55-year-old man. One SCC lesion tested positive for human papillomavirus (HPV)-58. HPV-associated digital SCCs have been reported; most cases are HPV-16 positive. This report describes a rare case of an HPV-58-positive invasive digital SCC and an HPV-73-positive SCC in situ associated with ADPA.
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Adenocarcinoma Papilar/virologia , Carcinoma de Células Escamosas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Neoplasias Cutâneas/virologia , Adenocarcinoma Papilar/patologia , Biópsia , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/patologia , Dedos/patologia , Dedos/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/virologia , Papillomaviridae/classificação , Neoplasias Cutâneas/patologiaAssuntos
Canal Anal/virologia , Neoplasias do Ânus/prevenção & controle , Vacinas Anticâncer/uso terapêutico , Infecções por HIV/complicações , Infecções por Papillomavirus/complicações , Canal Anal/patologia , Neoplasias do Ânus/etiologia , Neoplasias do Ânus/patologia , Feminino , HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Papillomaviridae/imunologia , Infecções por Papillomavirus/virologia , Resultado do TratamentoRESUMO
BACKGROUND: The use of Sample-to-answer (STA) platforms for the detection of influenza A/B and respiratory syncytial virus (RSV) have greatly improved patient care. These diagnostic assays based on nucleic acid amplification are rapid, accurate and relatively easy to perform. OBJECTIVES: We compared four such platforms for detecting FluA, FluB, and RSV from adult respiratory specimens: Hologic Panther Fusion® Flu A/B/RSV (Fusion), Cobas® Influenza A/B & RSV (Liat), Luminex Aries® Flu A/B & RSV (Aries), and Diasorin SimplexaTM Flu A/B & RSV (Simplexa). STUDY DESIGN: Nasopharyngeal (NP) swabs (n = 224) from adults were tested on these platforms and results were compared to Center for Disease Control and Prevention recommended real-time RT-PCR assay for influenza A/B and RSV. Subtyping for FluA and FluB was performed for discrepant analysis where applicable. RESULTS: Of the 82 FluA, 26 FluB, 15 RSV-positive specimens tested, the positive and negative percentage agreements (PPA and NPA respectively) for FluA detection were 100/100 (Fusion), 95.1/100 (Liat), 92.5/100 (Aries), and 84.1/99.3 (Simplexa); PPA and NPA for FluB detection were 92.3/99.5 (Fusion), 96/99.5 (Liat), 100/99.5 (Aries), and 80.8/100 (Simplexa); and for RSV detection were 100/100 (Fusion), 100/100 (Liat), 88.6/99.5 (Aries), and 73.3/100 (Simplexa). 82 confirmed FluA included 23 pH1N1 and 57 H3N2 strains with 2 strains remaining untyped. Of the 26 confirmed FluB, 25 were of the Yamagata lineage and 1 of unknown lineage. CONCLUSION: Only 2 STA platforms demonstrated >95% PPA for the detection of all three targets while all the 4 platforms demonstrated >95% NPA for FluA, FluB and RSV.
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Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Nasofaringe/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vírus da Influenza A/genética , Vírus da Influenza B/genética , Masculino , Pessoa de Meia-Idade , Vírus Sincicial Respiratório Humano/genética , Estudos Retrospectivos , Adulto JovemRESUMO
Abdominal lymphangiectasia is a rare disease manifestation with a variety of anatomic locations and clinical presentations. The gastrointestinal tract may be affected, and lymphangiectasia originating in the wall of the intestine has rarely been described. We present a case of primary small bowel lymphangiectasia causing intussusception in a 30-year-old woman who presented with emesis and gastrointestinal bleeding. This case emphasizes the clinical presentation, diagnosis, and management in adults with abdominal lymphangiectasia. We highlight the importance of a high clinical suspicion for lymphangiectasia in an adult with acute abdomen to avoid catastrophic morbidity.
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This report is a case of a 58-year-old woman with a mixed ductal-endocrine carcinoma of the pancreas and a synchronous carcinoma-in-situ of the common bile duct. She presented with intractable itching from obstructive jaundice. Magnetic resonance imaging scan showed dilated intrahepatic biliary and common bile ducts. Endoscopic retrograde cholangiopancreatography revealed an ulcerated lesion of the ampulla. Biopsies from this lesion showed adenocarcinoma. Subsequently, pancreatoduodenectomy was performed for the diagnosis of peri-ampullary carcinoma. Gross examination revealed a 2-cm irregular, ulcerated lesion obstructing the distal 0.5 cm of the common bile duct within the head of the pancreas. On histopathological examination, it was discovered that this lesion contained two separate neoplasms: papillary carcinoma-in-situ of the intraparenchymal portion of the common bile duct and a mixed ductal-endocrine carcinoma of the pancreas. Mixed ductal-endocrine carcinoma of the pancreas is very rare. Finding it in conjunction with a synchronous, overlying papillary carcinoma carcinoma-in-situ of the common bile duct has not been previously described.
Assuntos
Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Pancreáticas/patologia , Carcinoma in Situ/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Pancreáticas/cirurgiaRESUMO
Rigid immobilization of the cervical spine in children is normally accomplished with a halo ring attached to the skull with pins. Concern exists about the risk of halo pin complications in small children due to their diminished skull thickness. More data are needed on biomechanical properties of the immature skull and on safe levels for halo pin penetration forces. The study included halo pin penetration tests on 43 skull samples obtained from eight fetal calves, radial compression tests of 11 skull samples, and histology. Compressive composite elastic modulus (15-139MPa), yield stress (1-5MPa) and composite consolidation modulus (188-479MPa) were measured in the skull's radial direction. Pin penetration force (F) in Newtons at a pin-penetration depth equal to the original skull thickness (T) in mm, was related to T as: F=100+4.3e(T) (R(2)=0.76, p<0.0001). However, the 95% confidence limits on individual predictions were wide, e.g., 0-475MPa for T=1.5mm and 0-700MPa for T=4mm. These results suggest that skull thickness cannot be reliably used to predict halo pin penetration loads in a skull with similar structural and mechanical properties to that of the fetal calf. Due to the lack of available human data for comparison, the relevance of using the fetal calf skull as a model for human infants and young children remains inconclusive. Clinical recommendations regarding pediatric halo pin penetration loads cannot be made without further study of children's skull structure and biomechanical properties.
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Fenômenos Biomecânicos , Pinos Ortopédicos , Modelos Animais , Crânio , Animais , Fenômenos Biomecânicos/métodos , Bovinos , FetoRESUMO
INTRODUCTION: Synovial hemangioma is a developmental hamartoma of vascular tissue within the synovium; no cases involving the shoulder girdle have been described in the literature. Synovial chondromatosis is a benign condition in which synovial cells undergo metaplasia into hyaline cartilage and is also thought to infrequently affect the shoulder region. CASE REPORT: A 44-year-old female presented with left shoulder pain of 7-year duration. Magnetic resonance image displayed a 2.5 cm × 2.5 cm lesion in the anterior glenohumeral joint, with hypointense T1- and hyperintense T2-weighted signal and peripheral and septal enhancement. Arthroscopic biopsy of the synovial-appearing mass led to a histologic diagnosis of synovial hemangioma. Successful embolization was performed, and repeat arthroscopy then revealed a white consolidated mass at the subscapularis recess. After en bloc excision, histologic evaluation was consistent with synovial chondromatosis. At 6 months, she denied any pain or limitation in her shoulder. CONCLUSION: Synovial hemangioma has never before been reported to involve the shoulder region. Histologically, engorged inflammatory vessels secondary to a mass effect are identical to a hemangioma. The clinician should be aware that synovial chondromatosis or other masses may compress synovial vessels and histologically mimic a hemangioma.
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BACKGROUND: Angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) are known to be involved in fetoplacental angiogenesis adequacy, which is a primary determinant of fetal growth. Regional variations in Ang1, Ang2, and Tie2 remain unknown, although fetoplacental vascularity and gene expressions differ between the placental center and the periphery. OBJECTIVE: The aim of this study was to test the hypothesis that there are regional variations in the expression of these angiopoietins in human placentas from uncomplicated term and near term pregnancies. STUDY DESIGN: In this prospective study, central and peripheral samples were collected from fresh placentas from normal-term and near-term pregnancies delivered by Cesarean section (n = 7, 36-41 week gestation) prior to the onset of labor. Regional differences in Ang1, Ang2, and Tie2 protein expressions were measured by Western blot and densitometric analyses with b-actin normalization, and their fetoplacental regional localization assessed by immunohistochemistry. The Ang1 and Ang2 ratios at central and peripheral sites were determined. Statistical analysis was performed using Student's t-test. RESULTS: Ang1 protein expression was higher in the placental periphery than in the center (2.48 ± 0.42 versus 1.74 ± 0.27, p = 0.01). In contrast, Ang2 protein expression was greater in the placental center than in the periphery (10.10 ± 1.82 versus 7.15 ± 1.12, respectively, p = 0.03). The Ang1-Ang2 ratio reflected these differential expressions. Tie2 protein expression was higher in the placental periphery than in the center (0.21 ± 0.02 versus 0.16 ± 0.02, p = 0.003). The immunoreactivity of Ang1 and Tie2 was stronger in the periphery than in the center, and that of Ang2 was stronger in the center than in the periphery. CONCLUSIONS: Ang1, Ang2, and Tie2 are differentially expressed in placental center and periphery. Ang1/Ang2 ratio reflects this regional variation in the angiogenic balance that has implications for fetoplacental villous angiogenesis. The results also demonstrate the importance of considering the location of placental sampling sites for any future investigations of fetoplacental villous angiogenesis.
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Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Neovascularização Patológica/metabolismo , Placenta/irrigação sanguínea , Receptor TIE-2/metabolismo , Angiopoietina-1/genética , Angiopoietina-2/genética , Western Blotting , Feminino , Retardo do Crescimento Fetal/metabolismo , Humanos , Circulação Placentária , Gravidez , Estudos Prospectivos , Receptor TIE-2/genéticaRESUMO
BACKGROUND: Pulmonary fat embolism (FE) in patients after major bone fracture and other trauma may lead to acute respiratory distress, but few clinical evidence of lung injury remains, and there is a dearth of histopathologic information after the initial recovery. We recently reported histologic changes in the lungs of a patient who died after cesarian delivery, which were similar to a rat model of FE. In this model, we found that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time, an additional insult could exacerbate the effects. METHODS: Triolein (0.2 mL intravenously administered) was given to 18 rats and saline to 18 controls. Six weeks later, each group received (intraperitoneal) lipopolysaccharide (LPS, 3 mg/kg; n = 9) or saline (n = 9). At necropsy 48 hours later, lungs and organs were harvested for study. Lung parenchymal, vascular, and bronchial damage was scored by two pathologists and by Image J analysis. RESULTS: Animals given LPS after triolein showed reduced pulmonary arterial medial diameters compared with those that received LPS alone (p < 0.04). Lung small arterial patency (lumen) was reduced after triolein and even more after combined LPS and triolein (p = 0.018). Triolein increased fibrotic markers (trichrome and smooth muscle actin staining), and this was more severe after LPS. At 6 weeks, fat droplets remained in the lungs, localizing to the subpleural septa. These were smaller and more widespread after LPS. CONCLUSION: This report describes an animal model to study exacerbation of lung histopathology induced by FE using a known pulmonary toxicant, LPS (a "second hit"). Vascular and fibrotic lung damage was more severe when LPS was given to rats 6 weeks after triolein compared with LPS alone. FE rendered the lungs extra sensitive to a second hit long after apparent clinical recovery. This experimental model of fat embolism provides useful informations for the treatment of patients suffering for similar conditions.
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Embolia Gordurosa/complicações , Lipopolissacarídeos , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Trioleína , Grau de Desobstrução Vascular/efeitos dos fármacosRESUMO
BACKGROUND: Fat embolism (FE) after trauma and some orthopedic procedures is known to cause acute lung injury, including acute respiratory distress syndrome. However, its potential long-term effects on the lung are unknown. A previous study using a rat model of FE found significant histopathologic changes in the lungs after intravenous injection of triolein for up to 11 days. This study detailed the persistence of the lung damage and investigated the input of the renin-angiotensin system in its pathology. METHODS: Unanesthetized rats were injected via the tail vein with 0.2 mL saline or triolein. After euthanasia, at 3 weeks or 6 weeks, lung sections were stained to highlight cellular structure, presence of collagen and fat, or immunolabeled for smooth muscle actin or angiotensin peptides. RESULTS: At 3 weeks or 6 weeks after triolein injection, there was no dilatation of the heart or inferior vena cava, no congestion of the liver or spleen, no adventitial edema, nor was fluid present in alveoli or pleural cavity as reported in animals at earlier time points. Persisting pathology included reduced lumen patency, thickening of the media of small arteries and arterioles, and vascular and septal inflammation. Although the fat content of the lung decreased from week 3 to week 6, there was a progressive increase in collagen, smooth muscle actin, and angiotensin peptides. CONCLUSIONS: This model extends the effect of FE on pulmonary pathology to 6 weeks, revealing persistent vasculitis, septal inflammation, and progressive fibrotic changes which are associated with increased presence of angiotensin peptides.
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Embolia Gordurosa/complicações , Fibrose Pulmonar/etiologia , Angiotensinas/metabolismo , Animais , Colágeno/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Gorduras/análise , Pulmão/química , Pulmão/patologia , Masculino , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Women with low grade squamous intraepithelial lesions (LSIL) at cervical cancer screening are currently referred for further diagnostic work up despite 80% having no precancerous lesion. The primary purpose of this study is to measure the test characteristics of 3q26 chromosome gain (3q26 gain) as a host marker of carcinogenesis in women with LSIL. A negative triage test may allow these women to be followed by cytology alone without immediate referral to colposcopy. METHODS AND FINDINGS: A historical prospective study was designed to measure 3q26 gain from the archived liquid cytology specimens diagnosed as LSIL among women attending colposcopy between 2007 and 2009. 3q26 gain was assessed on the index liquid sample; and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were measured at immediate triage and at 6-16 months after colposcopic biopsy. The sensitivity of 3q26 gain measured at immediate triage from automated and manually reviewed tests in 65 non-pregnant unique women was 70% (95% CI: 35, 93) with a NPV of 89% (95% CI: 78, 96). The sensitivity and NPV increased to 80% (95% CI: 28, 99) and 98% (95% CI: 87, 100), respectively, when only the automated method of detecting 3q26 gain was used. CONCLUSIONS: 3q26 gain demonstrates high sensitivity and NPV as a negative triage test for women with LSIL, allowing possible guideline changes to routine surveillance instead of immediate colposcopy. Prospective studies are ongoing to establish the sensitivity, specificity, PPV and NPV of 3q26 gain for LSIL over time.
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Cromossomos Humanos Par 3 , Amplificação de Genes , Triagem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genética , Adulto , Colposcopia , Feminino , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
The pathophysiology of Fat Embolism Syndrome (FES) is poorly understood and subject to some controversy. Evaluation of the evolution of histological changes in the lungs of patients with FES is impractical. The current theories of FES were established through acute clinical observations and acute animal experiments, but sequential changes in the histology of lungs over a prolonged period have not been made. The progressive effects of fat embolization of the lungs were examined in a rat model over a period of 11 days. Triolein, a major bone marrow fat, was administered to conscious Sprague-Dawley rats via the caudal vein. Rats were euthanized at 24, 48, 96 h, and 11 days, but some died within a few hours. Histomorphometric evaluations of lung tissue were made, including stains for fat, collagen, and smooth muscle actin. Arterial and arteriolar patency decreased progressively up to 96 h, but returned toward normal after 11 days. A striking finding was the very early presence of inflammation and fibrosis after only several hours, persisting up to 11 days. The results of this study provide evidence of both very early and prolonged changes due to fat embolization.
Assuntos
Progressão da Doença , Embolia Gordurosa/complicações , Embolia Gordurosa/patologia , Embolia Pulmonar/etiologia , Embolia Pulmonar/patologia , Animais , Modelos Animais de Doenças , Fibrose/patologia , Pulmão/patologia , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Infiltrating myoepithelial carcinoma remains a rarely encountered lesion of the breast. The few cases that have surfaced firmly document the histopathology of this tumor, but its cytologic characteristics seemingly have been described in only one other report. CASE PRESENTATION: Here we present the cytologic findings from a case of infiltrating myoepithelial carcinoma of the breast in a 52-year-old female and provide a histologic correlation with the subsequent biopsy and mastectomy specimens. While the cytology specimens displayed more myoepithelial cellular heterogeneity than was present on histology, a number of cytologic features including hypercellularity, pleomorphic spindle cells, and mitotic activity correlated well with the histopathology. CONCLUSION: The role of fine needle aspiration in the diagnosis of mammary myoepithelial carcinoma, in this case, was to establish malignancy rather than to arrive at a specific diagnosis, as a number of different entities potentially can mimic this neoplasm on cytologic specimens.