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1.
Res Social Adm Pharm ; 20(5): 531-538, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38413289

RESUMO

BACKGROUND: Most breastfeeding individuals take at least one prescription drug, yet limited data from lactation studies are available to inform the safety of these drugs during breastfeeding. As a result, healthcare providers (HCPs) rely on available information about safety of drugs used during pregnancy or on personal experiences to inform prescribing/counseling decisions for breastfeeding individuals. To improve risk communication regarding drugs used during lactation, the U.S. Food and Drug Administration published the Pregnancy and Lactation Labeling Rule (PLLR) in 2015, which added a narrative summary of available risk information to the lactation section of Prescribing Information (PI). Prior studies on labeling in PLLR format revealed that although HCPs found these details valuable, they regarded the narrative as too long to support decision-making during patient encounters. OBJECTIVE: This qualitative study's objective was to assess the utility of adding a concise summary to the Lactation subsection of PI to complement the narrative and succinctly communicate to busy HCPs a drug's risks when used during lactation. The concise summary consisted of a bolded headline, bulleted descriptions of available study findings and potential adverse reactions, and recommendations for risk mitigation. METHODS: Twenty-five online focus groups were conducted with five segments of HCPs to obtain their feedback on the concise summary and discuss their prescribing/counseling decisions for four fictitious prescription drugs including one vaccine. RESULTS: HCPs utilized the concise summary to make initial prescribing/counseling decisions. Many also used the labeling narrative for a comprehensive benefit-risk assessment. CONCLUSION: The findings indicate a need to continue to improve communication about safety of drugs used during lactation, and that the concise summary may help facilitate this communication. The study also highlights the need to educate HCPs about PI limitations when clinical data are lacking and the need to encourage clinical studies to be conducted to support actionable recommendations about use of prescription drugs during lactation.


Assuntos
Lactação , Medicamentos sob Prescrição , Gravidez , Feminino , Humanos , Aleitamento Materno , Medicamentos sob Prescrição/efeitos adversos , Grupos Focais , Pessoal de Saúde
2.
JAMA Intern Med ; 183(9): 1015-1016, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37399033

RESUMO

This case series uses postmarketing data to evaluate the incidence of injection site necrosis after 23-valent pneumococcal vaccine use in the global market.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Lactente , Vacinas Pneumocócicas/efeitos adversos , Necrose , Infecções Pneumocócicas/prevenção & controle
3.
Clin Transl Gastroenterol ; 14(8): e00591, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37114910

RESUMO

INTRODUCTION: Behçet's disease (BD) is a chronic systemic vasculitis characterized by oral and genital ulcers, uveitis, and skin lesions. Patients with BD may develop gastrointestinal (GI) disease; however, characterization of GI disease in American cohorts is lacking. In this article, we present clinical, endoscopic, and histopathologic GI findings in an American cohort of patients with BD. METHODS: Patients with established BD were evaluated prospectively at the National Institutes of Health. Demographic and clinical data were collected including BD manifestations and GI symptoms. Endoscopy with histopathologic sampling was performed for both clinical and research indications with written consent. RESULTS: Eighty-three patients were evaluated. The majority were female (83.1%) and white (75.9%). Mean age was 36 ± 14.8 years. GI symptoms were reported in 75% of cohort with nearly half of reporting abdominal pain (48.2%) and significant numbers reporting acid reflux, diarrhea, and nausea/vomiting. Esophagogastroduodenoscopy was performed in 37 patients; erythema and ulcers were the most common found abnormalities. Colonoscopy was performed in 32 patients with abnormalities including polyps, erythema, and ulcers. Endoscopy was normal in 27% of esophagogastroduodenoscopies and 47% of colonoscopies. Vascular congestion was demonstrated on the majority of random biopsies throughout the GI tract. Inflammation was not highly prevalent on random biopsies except in the stomach. Wireless capsule endoscopy was performed on 18 patients; ulcers and strictures were the most common abnormalities. DISCUSSION: GI symptoms were common in this cohort of American patients with BD. Endoscopic examination was often normal; however, histopathologic examination demonstrated vascular congestion throughout the GI tract.


Assuntos
Síndrome de Behçet , Endoscopia por Cápsula , Gastroenteropatias , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/patologia , Úlcera , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Colonoscopia
4.
Pediatrics ; 151(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37082919

RESUMO

BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Adolescente , Criança , Humanos , Sistemas de Notificação de Reações Adversas a Medicamentos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Estados Unidos/epidemiologia , Vacinas/efeitos adversos
6.
Vaccine ; 40(24): 3389-3394, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35489985

RESUMO

BACKGROUND: Pregnant persons are at increased risk of severe illness from COVID-19 infection, including intensive care unit admission, mechanical ventilation, and death compared with non-pregnant persons of reproductive age. Limited data are available on the safety of COVID-19 vaccines administered during and around the time of pregnancy. OBJECTIVE: To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system, in pregnant persons who received a COVID-19 vaccine to assess for potential vaccine safety problems. METHODS: We searched VAERS for US reports of adverse events (AEs) in pregnant persons who received a COVID-19 vaccine from 12/14/2020-10/31/2021. Clinicians reviewed reports and available medical records. Crude reporting rates for selected AEs were calculated, and disproportional reporting was assessed using data mining methods. RESULTS: VAERS received 3,462 reports of AEs in pregnant persons who received a COVID-19 vaccine; 1,831 (52.9%) after BNT162b2, 1,350 (38.9%) after mRNA-1273, and 275 (7.9%) after Ad26.COV2.S. Eight maternal deaths and 12 neonatal deaths were reported. Six-hundred twenty-one (17.9%) reports were serious. Pregnancy-specific outcomes included: 878 spontaneous abortions (<20 weeks), 101 episodes of vaginal bleeding, 76 preterm deliveries (<37 weeks), 62 stillbirths (≥20 weeks), and 33 outcomes with birth defects. Crude reporting rates for preterm deliveries and stillbirths, as well as maternal and neonatal mortality rates were below background rates from published sources. No disproportional reporting for any AE was observed. CONCLUSIONS: Review of reports to VAERS following COVID-19 vaccines in pregnant persons did not identify any concerning patterns of maternal or infant-fetal outcomes.


Assuntos
COVID-19 , Vacinas , Ad26COVS1 , Sistemas de Notificação de Reações Adversas a Medicamentos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Natimorto/epidemiologia , Estados Unidos/epidemiologia
7.
Dig Dis Sci ; 67(5): 1831-1842, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-33934254

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency which can lead to gastrointestinal (GI) complications including inflammatory bowel disease. Radiographic findings in this cohort have not been well described. AIMS: To describe the frequency and spectrum of gastrointestinal abnormalities seen on computed tomography (CT) in patients with CGD and determine whether radiography was predictive of endoscopic or histopathologic inflammatory findings. METHODS: A retrospective review was conducted on 141 consecutive CGD patients seen at the National Institutes of Health between 1988 and 2011. All corresponding CTs were reviewed for gastrointestinal abnormalities including wall thickening. Endoscopic and histopathologic findings were reviewed in subjects with documented endoscopy within 30 days of an imaging study. Findings were compared between patients with and without wall thickening on CT to determine whether bowel wall thickening was predictive of endoscopic or histologic inflammatory findings. RESULTS: Two hundred and ninety-two CTs were reviewed. GI wall thickening was present on CT in 61% of patients (n = 86). Among a subgroup of 20 patients who underwent endoscopy at the time of their imaging, there was a statistically significant correlation between radiographic gastrointestinal wall thickening and endoscopic inflammation in the same intestinal segment (p = 0.035). Additionally, there was a significant correlation between radiographic gastrointestinal wall thickening and inflammatory features on histopathology (p = 0.02). CONCLUSIONS: GI abnormalities are commonly observed on CT in CGD patients. Bowel wall thickening correlates with endoscopic and histopathologic evidence of inflammation. These findings may be used to better facilitate directed endoscopic assessment and histopathologic sampling in patients with CGD.


Assuntos
Gastroenteropatias , Doença Granulomatosa Crônica , Endoscopia Gastrointestinal , Gastroenteropatias/complicações , Gastroenteropatias/etiologia , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico por imagem , Humanos , Inflamação/complicações , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
8.
JAMA ; 326(16): 1606-1613, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34617967

RESUMO

Importance: As part of postauthorization safety surveillance, the US Food and Drug Administration (FDA) has identified a potential safety concern for Guillain-Barré syndrome (GBS) following receipt of the Ad26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccine. Objective: To assess reports of GBS received in the Vaccine Adverse Event Reporting System (VAERS) following Ad26.COV2.S vaccination. Design, Setting, and Participants: Reports of presumptive GBS were identified in a US passive reporting system (VAERS) February-July 2021 and characterized, including demographics, clinical characteristics, and relevant medical history. Exposures: Receipt of the Ad26.COV2.S vaccine; the comparator was the background rate of GBS in the general (unvaccinated) population that had been estimated and published based on a standardized case definition. Main Outcomes and Measures: Presumptive GBS; the reporting rate was analyzed, including calculation of the observed to expected ratio based on background rates and vaccine administration data. Because of limited availability of medical records, cases were not assessed according to the Brighton Collaboration criteria for GBS. Results: As of July 24, 2021, 130 reports of presumptive GBS were identified in VAERS following Ad26.COV2.S vaccination (median age, 56 years; IQR, 45-62 years; 111 individuals [86.0%] were < 65 years; 77 men [59.7%]). The median time to onset of GBS following vaccination was 13 days (IQR, 10-18 days), with 105 cases (81.4%) beginning within 21 days and 123 (95.3%) within 42 days. One hundred twenty-one reports (93.1%) were serious, including 1 death. With approximately 13 209 858 doses of vaccine administered to adults in the US, the estimated crude reporting rate was 1 case of GBS per 100 000 doses administered. The overall estimated observed to expected rate ratio was 4.18 (95% CI, 3.47-4.98) for the 42-day window, and in the worst-case scenario analysis for adults 18 years or older, corresponded to an estimated absolute rate increase of 6.36 per 100 000 person-years (based on a rate of approximately 8.36 cases per 100 000 person-years [123 cases per 1 472 162 person-years] compared with a background rate of approximately 2 cases per 100 000 person-years). For both risk windows, the observed to expected rate ratio was elevated in all age groups except individuals aged 18 through 29 years. Conclusions and Relevance: These findings suggest a potential small but statistically significant safety concern for Guillain-Barré syndrome following receipt of the Ad26.COV2.S vaccine. However, the findings are subject to the limitations of passive reporting systems and presumptive case definition, and they must be considered preliminary pending analysis of medical records to establish a definitive diagnosis.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndrome de Guillain-Barré/epidemiologia , Ad26COVS1 , Adulto , Distribuição por Idade , Idoso , Vacinas contra COVID-19/administração & dosagem , Feminino , Síndrome de Guillain-Barré/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados Preliminares , Vigilância de Produtos Comercializados , Estados Unidos/epidemiologia , Vacinação/estatística & dados numéricos , Adulto Jovem
9.
MMWR Morb Mortal Wkly Rep ; 70(32): 1094-1099, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34383735

RESUMO

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Imunização/normas , Guias de Prática Clínica como Assunto , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Comitês Consultivos , COVID-19/epidemiologia , Aprovação de Drogas , Humanos , Estados Unidos/epidemiologia , Vacinas Sintéticas , Vacinas de mRNA
10.
N Engl J Med ; 384(24): 2273-2282, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33882218

RESUMO

BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Gravidez , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Pessoa de Meia-Idade , Nascimento Prematuro/epidemiologia , Vigilância em Saúde Pública/métodos , Sistema de Registros , Estados Unidos/epidemiologia , Vacinas Sintéticas/efeitos adversos , Adulto Jovem , Vacinas de mRNA
11.
PLoS One ; 12(10): e0175484, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28981524

RESUMO

Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1) do mutations in the target/pathway confer resistance? (2) Are these mutations pre-existing? (3) What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC). We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g) and regression (d, decay) of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor) antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Análise Mutacional de DNA , Receptores ErbB/metabolismo , Evolução Molecular , Deriva Genética , Humanos , Mutação , Panitumumabe , Proteínas Proto-Oncogênicas p21(ras)/metabolismo
12.
Drug Saf ; 40(7): 571-582, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28293864

RESUMO

INTRODUCTION: Duplicate case reports in spontaneous adverse event reporting systems pose a challenge for medical reviewers to efficiently perform individual and aggregate safety analyses. Duplicate cases can bias data mining by generating spurious signals of disproportional reporting of product-adverse event pairs. OBJECTIVE: We have developed a probabilistic record linkage algorithm for identifying duplicate cases in the US Vaccine Adverse Event Reporting System (VAERS) and the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: In addition to using structured field data, the algorithm incorporates the non-structured narrative text of adverse event reports by examining clinical and temporal information extracted by the Event-based Text-mining of Health Electronic Records system, a natural language processing tool. The final component of the algorithm is a novel duplicate confidence value that is calculated by a rule-based empirical approach that looks for similarities in a number of criteria between two case reports. RESULTS: For VAERS, the algorithm identified 77% of known duplicate pairs with a precision (or positive predictive value) of 95%. For FAERS, it identified 13% of known duplicate pairs with a precision of 100%. The textual information did not improve the algorithm's automated classification for VAERS or FAERS. The empirical duplicate confidence value increased performance on both VAERS and FAERS, mainly by reducing the occurrence of false-positives. CONCLUSIONS: The algorithm was shown to be effective at identifying pre-linked duplicate VAERS reports. The narrative text was not shown to be a key component in the automated detection evaluation; however, it is essential for supporting the semi-automated approach that is likely to be deployed at the Food and Drug Administration, where medical reviewers will perform some manual review of the most highly ranked reports identified by the algorithm.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Interpretação Estatística de Dados , Mineração de Dados , Bases de Dados Factuais , Humanos , Estados Unidos
13.
Surgery ; 161(1): 230-239, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27839933

RESUMO

BACKGROUND: A staging/prognostic system has long been desired to better categorize pheochromocytoma/paraganglioma which can be very aggressive in the setting of SDHB mutations. METHODS: A retrospective analysis was conducted of clinical characteristics and outcomes including results of genetic testing, tumor recurrence/metastasis, Ki67/MIB1% staining, and tumor mitotic index in patients with pheochromocytoma/paraganglioma. RESULTS: Patients with SDHB mutation presented at younger age (33.0 years old vs 49.6 years old, P < .001), had increased local recurrence and distant metastases (47.6% vs 9.1%, P < .001, and 56.3% vs 9.1%, P < .001, respectively), and lesser median disease-free interval (89.8 months, 95% confidence interval 36.0-96.4 vs not reached, P < .001). SDHB mutation, greatest tumor diameter, and open operative resection were associated with a greater rate of local recurrence and distant metastases (P < .006 each). SDHB mutation and tumor diameter were independent risk factors for local recurrence (P ≤ .04 each) and metastases. Ki67% and mitotic index were not associated with SDHB mutation (P ≥ .09 each), local recurrence (P = .48, P = .066, respectively), metastases (P ≥ .22 each), or disease-free interval (P ≥ .19 each). CONCLUSION: SDHB status and primary tumor size are more predictive of patient outcome than Ki67% or mitotic index and should be part of any clinically relevant, prognostic scoring system.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Mutação em Linhagem Germinativa , Paraganglioma/genética , Feocromocitoma/genética , Succinato Desidrogenase/genética , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Biópsia por Agulha , Estudos de Coortes , Bases de Dados Factuais , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/patologia , Neoplasias do Sistema Digestório/cirurgia , Intervalo Livre de Doença , Feminino , Testes Genéticos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Paraganglioma/mortalidade , Paraganglioma/patologia , Paraganglioma/cirurgia , Feocromocitoma/mortalidade , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Carga Tumoral
14.
Clin Neuropathol ; 35(2): 78-83, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26709712

RESUMO

Although schwannoma and neurofibroma tumors are generally reported as distinct pathologic diagnoses, sporadic schwannoma/neurofibroma hybrid nerve sheath tumors have been reported in the general population with components of both entities. We report the clinicopathological features of these hybrid nerve sheath tumors in patients with neurofibromatosis type 2 (NF2). A retrospective review of nerve sheath tumor surgical specimens from patients with NF2 enrolled at the National Institutes of Health was performed. Those specimens reported to have schwannoma-like and neurofibromalike features were selected for further characterization by morphology, immunohistochemical panel (CD34, S100, neurofilament triplet protein (immunostain) (NFTP), epithelial membrane antigen (EMA)), and confirmation as hybrid tumors. Of 43 total NF2 patients undergoing resection of nerve sheath tumors, 11 specimens from 11 (26%) patients were found to be benign nerve sheath tumors exhibiting hybrid features of both neurofibroma and schwannoma. Immunohistochemical studies showed the schwannoma component to be S100+, CD 34- while the neurofibroma component was CD34+, variable S100+. Our experience emphasizes the importance of including this distinct tumor subtype, the schwannoma/neurofibroma hybrid tumor, in the differential diagnosis of nerve sheath tumors in NF2 patients and suggests that the relationship between neurofibroma and schwannoma tumors is closer than previously suspected..


Assuntos
Neurilemoma/patologia , Neurofibroma/patologia , Neurofibromatose 2/patologia , Adolescente , Biomarcadores Tumorais/análise , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Ann Surg Oncol ; 22 Suppl 3: S676-82, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26350374

RESUMO

BACKGROUND: Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as (68)Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using (68)Ga-DOTATATE in patients with primary and recurrent GEPNETs. METHODS: Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with (68)Ga-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed. RESULTS: The median decay corrected target count rate was 172.6 (range 28.15-2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6-43.56). The median lesion size was 1.55 (range 0.5-15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUVmax) of the lesions and TBR (Spearman r = - 0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUVmax and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6-40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS. CONCLUSIONS: Our study shows that RGS with (68)Ga-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with (68)Ga-DOTATATE.


Assuntos
Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/cirurgia , Imagem Multimodal/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Compostos Organometálicos/farmacocinética , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Compostos Radiofarmacêuticos/farmacocinética , Radioterapia Guiada por Imagem/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Biomarcadores Tumorais , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Técnicas Imunoenzimáticas , Neoplasias Intestinais/metabolismo , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Distribuição Tecidual , Tomografia Computadorizada por Raios X/métodos
16.
Appl Immunohistochem Mol Morphol ; 22(5): 358-62, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24805132

RESUMO

Angiosarcoma (AS) is a rare malignant vascular tumor, whereas epithelioid hemangioendothelioma (EHE) is a vascular tumor of low-grade malignancy. CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). Although the expression of CD30 is most commonly associated with lymphoid malignancies or germ cell tumors, occasional ASs have been reported as CD30 positive. However, there are limited data to evaluate its role definitively in malignant vascular tumors. In this study, we evaluated 91 ASs, 30 EHEs from various sites, and 25 Kaposi sarcomas. Overall, CD30 was expressed in 31/91 cases (34%) of AS, in 7/30 cases (30%) of EHE, but in none of the Kaposi sarcomas. CD30 was expressed in a membranous staining pattern and positivity in tumor cells varied from focal to diffuse. The positive ASs included vasoformative more differentiated tumors and also solid, undifferentiated, lymphoma-like examples, one of which was classified as lymphoma before the era of immunohistochemistry. The CD30 expression was seen in >50% of tumor cells in a majority of ASs but only in 7% of EHEs. None of the 55 ASs studied were immunohistochemically positive for TIA-1 or Granzyme B, antigens used as more specific markers for anaplastic large-cell lymphoma. Compared with AS, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30 positivity, whereas in most other hemangiomas, CD30 positivity was scant. In conclusion, CD30 expression occurs in a significant subset of ASs and EHEs and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive ASs could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates.


Assuntos
Hemangioendotelioma Epitelioide/diagnóstico , Antígeno Ki-1/metabolismo , Neoplasias de Tecido Vascular/diagnóstico , Receptores do Fator de Necrose Tumoral/metabolismo , Sarcoma de Kaposi/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinogênese , Diferenciação Celular , Criança , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Hemangioendotelioma Epitelioide/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Vascular/metabolismo , Sarcoma de Kaposi/metabolismo , Adulto Jovem
17.
J Clin Microbiol ; 52(7): 2726-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24829241
18.
Urol Case Rep ; 2(2): 39-62, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24696789

RESUMO

Forty -five year-old man with left renal mass underwent nephrectomy to reveal 20cm tumor diagnosed as sarcomatoid chromophobe renal cell carcinoma (CRCC). Lymph node metastasis of chromophobe and sarcomatoid components, disseminated tumor in retroperitoneal fat, lymphatic vessels, peri-renal adipose tissue in lymphangitic carcinomatosis pattern were identified. Chromophobe epithelial cells EMA, c-Kit, cytokeratin 7 positive; sarcomatoid cells were CD10, SMA positive with high proliferation index . Chromophobe epithelial cells had loss of heterozygosity (LOH) in chromosomes 1p, 1q while sarcomatoid cells had LOH in 3p,1p, 1q. In conclusion, sarcomatoid CRCC has aggressive biologic behavior and potential to metastasize in unusual patterns.

19.
Transfusion ; 54(7): 1712-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24588210

RESUMO

BACKGROUND: In experimental pneumonia we found that transfused older blood increased mortality and lung injury that was associated with increased in vivo hemolysis and elevated plasma cell-free hemoglobin (CFH), non-transferrin-bound iron (NTBI), and plasma labile iron (PLI) levels. In this study, we additionally analyze identically treated animals that received lower or higher bacterial doses. STUDY DESIGN AND METHODS: Two-year-old purpose-bred beagles (n = 48) challenged intrabronchially with Staphylococcus aureus (0 [n = 8], 1.0 × 10(9) [n = 8], 1.25 × 10(9) [n = 24], and ≥1.5 × 10(9) [n = 8] colony-forming units/kg) were exchange transfused with either 7- or 42-day-old canine universal donor blood (80 mL/kg in four divided doses). RESULTS: The greater increases in CFH with older blood over days after exchange proved relatively independent of bacterial dose. The lesser increases in CFH observed with fresher blood were bacterial dose dependent potentially related to bacterial hemolysins. Without bacterial challenge, levels of CFH, NTBI, and PLI were significantly higher with older versus fresher blood transfusion but there was no significant measurable injury. With higher-dose bacterial challenge, the elevated NTBI and PLI levels declined more rapidly and to a greater extent after transfusion with older versus fresher blood, and older blood was associated with significantly worse shock, lung injury, and mortality. CONCLUSION: The augmented in vivo hemolysis of transfused older red blood cells (RBCs) appears to result in excess plasma CFH and iron release, which requires the presence of established infection to worsen outcome. These data suggest that transfused older RBCs increase the risks from infection in septic subjects.


Assuntos
Lesão Pulmonar Aguda/etiologia , Preservação de Sangue/efeitos adversos , Transfusão Total/efeitos adversos , Pneumonia Estafilocócica/complicações , Staphylococcus aureus , Lesão Pulmonar Aguda/sangue , Animais , Modelos Animais de Doenças , Cães , Ferro/sangue , Pneumonia Estafilocócica/sangue , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
20.
J Am Coll Surg ; 218(5): 997-1003, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24661849

RESUMO

BACKGROUND: The natural history of pancreatic neuroendocrine neoplasms (PNENs) in patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of patients with PNENs is challenging because there are no reliable preoperative criteria to detect malignant lesions, and the majority of resected tumors are found to be benign. The aim of this study was to determine whether 18-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) uptake predicts growth and detects malignant VHL-associated PNENs. STUDY DESIGN: We performed a prospective study of 197 patients with VHL-associated pancreatic lesions. Clinical and imaging characteristics were analyzed to study the associations between FDG-PET uptake, tumor growth, and the development of metastatic disease. RESULTS: One hundred nine of 197 patients had solid pancreatic lesions and underwent both CT and (18)FDG-PET scanning, which identified 165 and 144 lesions, respectively. Metastatic disease was detected by (18)FDG-PET in 3 patients in whom it was not detected by CT scan and suggested non-neoplastic disease in 3 patients. Maximum standardized uptake values (SUV) on (18)FDG-PET correlated with tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated with tumor growth (r = 0.36, p = 0.0062). No association was seen between (18)FDG-PET uptake and age, VHL genotype, or serum chromogranin A levels. CONCLUSIONS: Scanning with FDG-PET identifies metastatic disease not detected by CT scan and avoids resection of non-PNEN lesions that have no malignant potential in patients with VHL-associated PNENs. It should be considered as a valuable functional imaging modality in the clinical management of patients with VHL-associated PNENs.


Assuntos
Fluordesoxiglucose F18 , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Doença de von Hippel-Lindau/diagnóstico por imagem , Adolescente , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/etiologia , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/cirurgia , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Adulto Jovem , Doença de von Hippel-Lindau/complicações
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