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1.
Med Sci Monit ; 30: e944714, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572571

RESUMO

The published grant number was "OFJH2021008", while the correct should read "DFJH2021008". Reference: Yinghong Wu, Huiling Liu, Minghao Zhong, Xiyi Chen, Zhiqiong Ba, Guibin Qiao, Jiejie Feng, Xiuqun Zeng: Enhanced Patient Comfort and Satisfaction with Early Oral Feeding after Thoracoscopic Lung Cancer Resection. Med Sci Monit, 2023; 29: e941577. DOI: 10.12659/MSM.941577.

2.
Med Sci Monit ; 29: e941577, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37953532

RESUMO

BACKGROUND The study aimed to compare the patient-reported outcomes in patients who underwent early vs conventional feeding after thoracoscopic lung cancer resection. MATERIAL AND METHODS The study enrolled 211 patients who underwent thoracoscopic lung cancer resection at a tertiary hospital between July 2021 and July 2022. Patients were randomly assigned to the conventional group or the early feeding group. There were 106 patients in the early feeding group and 105 patients in the conventional group. The conventional group received water 4 h after extubation and liquid/semi-liquid food 6 h after extubation. In contrast, the early feeding group received water 1 h after extubation and liquid/semi-liquid food 2 h after extubation. The primary outcomes were the degree of hunger, thirst, nausea, and vomiting. The secondary outcomes were postoperative complications, duration of hospital stay, and chest tube drainage. RESULTS No differences were found between the 2 groups in the degrees of postoperative nausea, vomiting, or pain after extubation for 1, 2, 4, and 8 h. Postoperative complications, duration of chest tube drainage, and duration of hospital stay were also similar (P=0.567, P=0.783, P=0.696). However, the hunger and thirst scores after extubation for 2 h and 4 h decreased and were lower in the early feeding group (both P<0.001). No patients developed choking, postoperative aspiration, gastrointestinal obstruction, or other complications. CONCLUSIONS Early oral feeding after thoracoscopic lung cancer resection is safe and can increase patient comfort postoperatively.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Conforto do Paciente , Satisfação do Paciente , Náusea e Vômito Pós-Operatórios/etiologia , Satisfação Pessoal , Água , Tempo de Internação
3.
J Magn Reson Imaging ; 56(3): 691-699, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35038210

RESUMO

BACKGROUND: Readout-segmented echo-planar diffusion-weighted imaging (RS-EPI) can improve image quality and signal-to-noise ratio, the resulting apparent diffusion coefficient (ADC) value acts as a more sensitive biomarker to characterize tumors. However, data regarding the differentiation of breast cancer (BC) receptor statuses using RS-EPI are limited. PURPOSE: To determine whether RS-EPI improves the differentiation of receptor statuses compared with conventional single-shot (SS) EPI in breast MRI. STUDY TYPE: Retrospective. POPULATION: A total of 151 BC women with the mean age of 50.6 years. FIELD STRENGTH/SEQUENCE: A 3 T/ RS-EPI and SS-EPI. ASSESSMENT: The ADCs of the lesion and normal background tissue from the two sequences were collected by two radiologists with 15 years of experience working of breast MRI (M.H.Z. and X.F.C.), and a normalized ADC was calculated by dividing the mean ADC value of the lesion by the mean ADC value of the normal background tissue. STATISTICAL TESTS: Agreement between the ADC measurements from the two sequences was assessed using the Pearson correlation coefficient and Bland-Altman plots. One-way analysis of variance, Kruskal-Wallis test, and median difference were used to compare the ADC measurements for all lesions and different receptor statuses. A P value less than 0.05 indicated a significant result. RESULTS: The ADC measurements of all lesions and normal background tissues were significantly higher on RS-EPI than on SS-EPI (1.82 ± 0.33 vs. 1.55 ± 0.30 and 0.83 ± 0.11 vs. 0.79 ± 0.10). The normalized ADC was lower on RS-EPI than on SS-EPI (0.47 ± 0.11 vs. 0.53 ± 0.12, a median difference of -0.04 [95% CI: -0.256 to 0.111]). For both diffusion methods, only the ADC measurement of RS-EPI was higher for human epidermal growth factor receptor-2 (HER-2)-positive tumors than for HER-2-negative tumors (0.87 ± 0.10 vs. 0.81 ± 0.11), and this measurement was associated with HER-2 positive status (adjusted odds ratio [OR] = 654.4); however, similar results were not observed for the ADC measurement of SS-EPI (0.80 ± 0.10 vs. 0.78 ± 0.11 with P = 0.199 and adjusted OR = 0.21 with P = 0.464, respectively). DATA CONCLUSION: RS-EPI can improve the distinction between HER-2-positive and HER-2-negative breast cancer, complementing the clinical application of diffusion imaging. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Razão Sinal-Ruído
4.
Pediatr Dev Pathol ; 23(6): 472-475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32924814

RESUMO

Primary lung adenocarcinomas are rare in pediatric patients, and even rarer in patients without precedent malignancy or congenital malformation. Here we present the first reported case of primary lung cribriform adenocarcinoma with squamoid morules in a previously healthy adolescent female. Molecular testing identified CTNNB1 mutation in the tumor and excluded other common mutations in lung adenocarcinoma. Our case suggests molecular alterations to the same signaling pathway can lead to similar histomorphology regardless of the tissue of origin.


Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/patologia , Pulmão/patologia , beta Catenina/genética , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/genética , Adolescente , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação
5.
Proc Natl Acad Sci U S A ; 112(38): 11965-70, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26372964

RESUMO

The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Apolipoproteína E4/metabolismo , Transtornos Cognitivos/complicações , Transtornos Cognitivos/metabolismo , Fosfolipídeos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Apolipoproteína E4/genética , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Técnicas de Introdução de Genes , Homeostase , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso , Neurônios/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Monoéster Fosfórico Hidrolases
6.
Ann Diagn Pathol ; 21: 7-11, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27040924

RESUMO

Increased telomerase activity is associated with almost all types of advanced human cancers with unknown molecular mechanism(s). Two recurrent point mutations in the promoter region of telomerase reverse transcriptase (TERT)--the key subunit of telomerase--have recently been identified in melanoma as well as a small sample of bladder cancer cell lines. However, the incidence and clinical-pathological significance of these mutations in urothelial carcinoma have not been well established yet. We collected 86 specimens of urothelial carcinoma including upper and lower urinary tract: high grade and low grade, invasive and noninvasive, and primary and metastatic. We also included some matched benign urothelium and common benign bladder lesions: cystitis, nephrogenic adenoma, and inverted papilloma. In addition, we collected urine samples for urothelial carcinoma workup; blood samples from patients underwent cystectomy with extensive lymphovascular invasion. All specimens were subject to polymerase chain reaction amplification and bidirectional Sanger sequencing for the TERT promoter mutations: C228T and C250T. We found that 64 (74%) of 86 carcinoma samples harbored 1 of the 2 TERT promoter mutations (C228T, n = 54; C250T, n = 10); the incidences were roughly equal regardless of site of origin, histologic grade, and invasive status. All matched benign and benign lesion samples showed wild-type sequence. These TERT promoter mutations are the most common genetic alterations in urothelial carcinoma and are not associated with tumor locations, grade, or invasiveness. Importantly, the feasibility of detecting these mutations in urine samples may provide a novel method to detect urothelial carcinoma in urine.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , Regiões Promotoras Genéticas/genética , Telomerase/genética , Neoplasias Urológicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNA , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias Urológicas/diagnóstico , Urotélio/patologia
7.
Genes Chromosomes Cancer ; 54(8): 500-505, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26032162

RESUMO

Xp11 (TFE3) translocation renal cell carcinoma (RCC) is officially recognized as a distinct subtype of RCC in the 2004 WHO classification. This neoplasm is characterized by several chromosomal translocations between the TFE3-involving Xp11.2 breakpoint and various fusion partners. To date, five partner genes have been identified, that is, PRCC in 1q21, PSF in 1q34, ASPL in 17q25, CLTC in 17q23, and NONO in Xq12; and three additional translocations have been reported with no partner gene being defined: t(X;3)(p11;q23), t(X;10)(p11;q23), and t(X;19)(p11;q13). Here, we report the identification of a novel TFE3 fusion partner, PARP14 in chromosome band3q21. We used RNA-seq on a 10-year-old FFPE (formalin-fixed, paraffin-embedded) tissue sample, which carried t(X;3)(p11;q23) as detected in the original cytogenetic study. The fusion transcript connected the 5'-end of the first two exons of PARP14 to the 3'-end of five exons of TFE3, which was verified by reverse transcription PCR (RT-PCR) and Sanger sequencing. Similar to other TFE3 fusions previously reported, the predicted PARP14-TFE3 product retains the nuclear localization and DNA-binding domains of TFE3. This finding expands the list of TFE3 translocation partner genes and re-emphasizes the essential oncogenic role of TFE3 fusion proteins in this tumor. Our result also clearly demonstrated the feasibility of identifying chromosomal translocation by RNA-seq in clinical FFPE, which are easily accessible and associated with valuable clinical information. © 2015 Wiley Periodicals, Inc.

8.
Ann Diagn Pathol ; 19(5): 301-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26239299

RESUMO

Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign to primary and secondary malignancies. The accurate diagnosis of these lesions is both important and challenging. Recently, studies suggest that telomerase reverse transcriptase (TERT) promoter mutations could be a biomarker for urothelial carcinoma (UC). We hypothesized that these mutations can distinguish UC with glandular differentiation from nephrogenic adenoma, primary adenocarcinoma of the urinary bladder (PAUB), or secondary malignancies. Twenty-five cases of benign glandular lesions (including nephrogenic adenoma); 29 cases of UC with glandular differentiation; 10 cases of PAUB; and 10 cases each of metastatic colon cancer, prostatic carcinoma, and carcinoma from Mullerian origin were collected. Slides were reviewed and selected to make sure the lesion was at least 10% to 20% of all tissue. Macrodissection was performed in some of cases, and genomic DNA was extracted from the tissue. Telomerase reverse transcriptase promoter mutations were determined by standard polymerase chain reaction sequencing. Twenty-one cases (72%) of UC with glandular differentiation were positive for TERT promoter mutations. However, none of the remaining cases (total 65 cases of benign lesions, PAUB, and metastatic carcinomas) was positive for TERT promoter mutation. Telomerase reverse transcriptase promoter mutations were highly associated with UC including UC with glandular differentiation but not other glandular lesions of bladder. Therefore, in conjunction with morphologic features, Immunohistochemistry stain profile, and clinical information, TERT promoter mutations could distinguish UC with glandular differentiation from other bladder glandular lesions. In addition, lack of TERT promoter mutations in primary adenocarcinoma of bladder suggests that this entity may have different origin or carcinogenesis from those of UC.


Assuntos
Mutação , Neoplasias Epiteliais e Glandulares/genética , Telomerase/genética , Doenças da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/genética , Adenoma/enzimologia , Adenoma/genética , Adenoma/patologia , Biomarcadores Tumorais/genética , Cistite/enzimologia , Cistite/genética , Cistite/patologia , Feminino , Humanos , Masculino , Neoplasias Epiteliais e Glandulares/enzimologia , Neoplasias Epiteliais e Glandulares/patologia , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Doenças da Bexiga Urinária/enzimologia , Doenças da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/secundário
9.
Ann Diagn Pathol ; 19(3): 146-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25862495

RESUMO

Squamous cell carcinoma (SCC) can arise from different anatomical sites including the skin, head and neck, lung, esophagus, genital area, and so on. Despite the same histopathologic features and immunohistochemistry profile, the SCCs of different body sites can show tremendous differences in their presenting symptoms, risk factor associations, natural history, prognosis, and response to treatment. This may reflect the fact that SCCs are heterogenous and likely have unique molecular characteristics at different anatomical sites. Recurrent somatic mutations in the TERT promoter region were first reported in human melanomas. Subsequently, other tumors including cutaneous SCC were found to demonstrate high frequencies of the same mutations. However, the incidences of TERT promoter mutation in noncutaneous SCCs have not been systemically studied. We investigated the TERT promoter mutation status among SCCs from different sites. We collected 84 cases of SCC from the skin (27), head and neck (12), lung (25), and cervix (10), as well as 10 cases of urothelial carcinoma with squamous differentiation (UC-SqD). We found that the frequencies of TERT promoter mutation among SCC of different sits are quite heterogenous: ~70% in skin SCC and UC-SqD, 16.67% in head and neck SCC, and 0% in lung and cervix SCC. These results may support the hypothesis of different carcinogenesis mechanisms of SCC in different sites. It also indicates that TERT promoter mutation could be a biomarker for distinguishing skin SCC or UC-SqD vs pulmonary SCC.


Assuntos
Carcinoma de Células Escamosas/genética , Mutação , Telomerase/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Melanoma/genética , Melanoma/patologia , Reação em Cadeia da Polimerase/métodos , Regiões Promotoras Genéticas , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
10.
J Biol Chem ; 288(44): 32050-63, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24052255

RESUMO

Recent studies link synaptojanin 1 (synj1), the main phosphoinositol (4,5)-biphosphate phosphatase (PI(4,5)P2-degrading enzyme) in the brain and synapses, to Alzheimer disease. Here we report a novel mechanism by which synj1 reversely regulates cellular clearance of amyloid-ß (Aß). Genetic down-regulation of synj1 reduces both extracellular and intracellular Aß levels in N2a cells stably expressing the Swedish mutant of amyloid precursor protein (APP). Moreover, synj1 haploinsufficiency in an Alzheimer disease transgenic mouse model expressing the Swedish mutant APP and the presenilin-1 mutant ΔE9 reduces amyloid plaque load, as well as Aß40 and Aß42 levels in hippocampus of 9-month-old animals. Reduced expression of synj1 attenuates cognitive deficits in these transgenic mice. However, reduction of synj1 does not affect levels of full-length APP and the C-terminal fragment, suggesting that Aß generation by ß- and γ-secretase cleavage is not affected. Instead, synj1 knockdown increases Aß uptake and cellular degradation through accelerated delivery to lysosomes. These effects are partially dependent upon elevated PI(4,5)P2 with synj1 down-regulation. In summary, our data suggest a novel mechanism by which reduction of a PI(4,5)P2-degrading enzyme, synj1, improves amyloid-induced neuropathology and behavior deficits through accelerating cellular Aß clearance.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Fragmentos de Peptídeos/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Monoéster Fosfórico Hidrolases/biossíntese , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação para Baixo/genética , Técnicas de Silenciamento de Genes , Hipocampo/patologia , Humanos , Lisossomos/genética , Lisossomos/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Fragmentos de Peptídeos/genética , Fosfatidilinositol 4,5-Difosfato/genética , Monoéster Fosfórico Hidrolases/genética , Presenilina-1/genética , Presenilina-1/metabolismo
11.
Mod Pathol ; 27(6): 875-86, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24309327

RESUMO

Xp11 translocation renal cell carcinomas harbor chromosome translocations involving the Xp11 breakpoint, resulting in gene fusions involving the TFE3 gene. The most common subtypes are the ASPSCR1-TFE3 renal cell carcinomas resulting from t(X;17)(p11;q25) translocation, and the PRCC-TFE3 renal cell carcinomas, resulting from t(X;1)(p11;q21) translocation. A formal clinical comparison of these two subtypes of Xp11 translocation renal cell carcinomas has not been performed. We report one new genetically confirmed Xp11 translocation renal cell carcinoma of each type. We also reviewed the literature for all published cases of ASPSCR1-TFE3 and PRCC-TFE3 renal cell carcinomas and contacted all corresponding authors to obtain or update the published follow-up information. Study of two new, unpublished cases, and review of the literature revealed that 8/8 patients who presented with distant metastasis had ASPSCR1-TFE3 renal cell carcinomas, and all but one of these patients either died of disease or had progressive disease. Regional lymph nodes were involved by metastasis in 24 of the 32 ASPSCR1-TFE3 cases in which nodes were resected, compared with 5 of 14 PRCC-TFE3 cases (P=0.02).; however, 11 of 13 evaluable patients with ASPSCR1-TFE3 renal cell carcinomas who presented with N1M0 disease remained disease free. Two PRCC-TFE3 renal cell carcinomas recurred late (at 20 and 30 years, respectively). In multivariate analysis, only older age or advanced stage at presentation (not fusion subtype) predicted death. In conclusion, ASPSCR1-TFE3 renal cell carcinomas are more likely to present at advanced stage (particularly node-positive disease) than are PRCC-TFE3 renal cell carcinomas. Although systemic metastases portend a grim prognosis, regional lymph node involvement does not, at least in short-term follow-up. The tendency for PRCC-TFE3 renal cell carcinomas to recur late warrants long-term follow-up.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas de Fusão Oncogênica/genética , Translocação Genética , Adolescente , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Proteínas de Ciclo Celular/genética , Cromossomos Humanos X/genética , Feminino , Heterogeneidade Genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias
12.
Int J Surg Pathol ; : 10668969241256109, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839260

RESUMO

Introduction. MYC overexpression is a known phenomenon in breast cancer. This study investigates the correlation of MYC gene copy number amplification and MYC protein overexpression with coexisting genetic abnormalities and associated clinicopathologic features in breast cancer patients. Methods. The study analyzed data from 81 patients with localized or metastatic breast cancers using targeted next-generation sequencing and MYC immunohistochemical studies, along with pathological and clinical data. Results. Applying the criteria of MYC/chromosome 8 ratio ≥5, MYC copy number amplified tumors (n = 11, 14%) were associated with invasive ductal carcinoma (91% vs 68%, P = .048), poorly differentiated (grade 3, 64% vs 30%, P = .032), mitotically active (Nottingham mitotic score 3, 71% vs 20%, P = .004), estrogen receptor (ER)-negative (45% vs 12%, P = .008), and triple-negative (56% vs 12%, P = .013) compared to MYC non-amplified tumors. Among MYC-amplified breast cancer patients, those with triple-negative status showed significantly shorter disease-free survival time than non-triple negative MYC-amplified patients (median survival month: 25.5 vs 127.6, P = .049). MYC amplification is significantly associated with TP53 mutation (P = .007). The majority (10 of 11; 91%) of MYC-amplified tumors showed positive c-MYC immunostaining. Conclusion. Breast cancers with MYC copy number amplication display distinct clinicopathologic characteristics indicative of more aggressive behavior.

13.
BMJ Open ; 14(9): e085733, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260857

RESUMO

OBJECTIVE: Pulmonary tuberculosis (PTB) is a critical challenge worldwide, particularly in China. This study aimed to explore the spatiotemporal transmission patterns and socioeconomic factors of PTB in Dongguan city, China. METHODS/DESIGN: An ecological study based on the reported new PTB cases between 2011 and 2020 was conducted in Dongguan city, China. The spatiotemporal analysis methods were used to explore the long-term trend, spatiotemporal transmission pattern and socioeconomic factors of PTB. MAIN OUTCOME MEASURES: The number of new PTB cases. PARTICIPANTS: We collected 35 756 new PTB cases, including 23 572 males and 12 184 females. RESULTS: The seasonal-trend decomposition indicated a significant downward trend for PTB with a significant peak in 2017 and 2018, and local spatial autocorrelation showed more and more high-high clusters in the central and north-central towns with high incidence. The multivariate spatial time series analysis revealed that the endemic component had a leading role in driving PTB transmission, with a high total effect value being 189.40 (95% CI: 171.65-207.15). A Bayesian spatiotemporal model revealed that PTB incidence is positively associated with the agricultural population ratio (relative risk (RR) =1.074), gender ratio (RR=1.104) and the number of beds in medical institutions (RR=1.028). CONCLUSIONS: These findings revealed potential spatiotemporal variability and spatial aggregation of PTB, so targeted preventive strategies should be made in different towns based on spatiotemporal transmission patterns and risk factors.


Assuntos
Fatores Socioeconômicos , Análise Espaço-Temporal , Tuberculose Pulmonar , Humanos , Tuberculose Pulmonar/epidemiologia , China/epidemiologia , Feminino , Masculino , Adulto , Incidência , Pessoa de Meia-Idade , Teorema de Bayes , Adulto Jovem , Fatores de Risco , Adolescente , Idoso
14.
Arch Pathol Lab Med ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39164013

RESUMO

CONTEXT.­: The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate. OBJECTIVE.­: To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas. DESIGN.­: Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model. RESULTS.­: In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes. CONCLUSIONS.­: Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.

15.
Commun Biol ; 7(1): 1171, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294434

RESUMO

Staphylococcus aureus (S. aureus) can cause various infections in humans and animals, contributing to high morbidity and mortality. To prevent and control cross-species transmission of S. aureus, it is necessary to understand the host-associated genetic variants. We performed a two-stage genome-wide association study (GWAS) including initial screening and further validation to compare genomic differences between human and pig S. aureus, aiming to identify host-associated determinants. Our multiple GWAS analyses found six consensus significant k-mers associated with host species, providing novel genetic evidence for distinguishing human from pig S. aureus. The best k-mer predictor achieved a high classification accuracy of 98.12% on its own and had extremely high resolution similar to the SNPs-based phylogeny, offering a very simple target for predicting the cross-species transmission risk of S. aureus. The final k-mer model revealed that 90% of S. aureus isolates from farm workers were predicted as livestock origin, suggesting a high risk of cross-species transmission. Bayesian inference revealed different cross-species transmission directions, with the human-to-pig transmission for ST5 and the pig-to-human transmission for ST398. Our findings provide a simple and accurate k-mer model for identifying and predicting the cross-species transmission risk of S. aureus.


Assuntos
Estudo de Associação Genômica Ampla , Infecções Estafilocócicas , Staphylococcus aureus , Doenças dos Suínos , Animais , Humanos , Suínos , Staphylococcus aureus/genética , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/transmissão , Infecções Estafilocócicas/veterinária , Estudo de Associação Genômica Ampla/métodos , Doenças dos Suínos/microbiologia , Genômica/métodos , Polimorfismo de Nucleotídeo Único , Filogenia , Teorema de Bayes , Genoma Bacteriano
16.
Pathol Res Pract ; 248: 154642, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37379711

RESUMO

OBJECTIVE: Diagnosis of inflammatory bowel disease (IBD)-associated dysplastic lesions can be challenging. This study aims to evaluate MYC immunohistochemistry (IHC) as a potential biomarker for IBD-associated dysplasia and compare its effectiveness with p53 IHC. METHODS: The study cohort included resections from 12 IBD patients with carcinoma and concurrent conventional low-grade dysplasia (LGD), as well as biopsies from 21 patients with visible conventional LGD, which were followed up for 2 years with subsequent endoscopic examination. MYC and p53 IHC and MYC-FISH analysis were performed. RESULTS: Sensitivity for LGD detection was 67% (8/12) and 50% (6/12) for MYC and p53, respectively, but the difference was not statistically significant (p = 0.2207). MYC and p53 overexpression were not always mutually exclusive, nor were they always present simultaneously. Patients who presented dysplasia in subsequent biopsies (7/21) were found to be more likely present with multiple LGD polyps and MYC-overexpressed LGD in the initial biopsies, compared to those without subsequent dysplasia (p < 0.05). These dysplastic lesions were commonly associated with chronic colitis (p = 0.0614). The distribution of LGD sites did not show a significant difference between patients with and without subsequent LGD. In MYC overexpressed cases, homogeneously strong nuclear expression was not identified in all dysplastic epithelial cells, and no MYC amplification was found in these cases by FISH. CONCLUSION: MYC IHC can complement p53 IHC as an adjunct biomarker for diagnosing IBD-associated conventional LGD and can be used for the prediction of subsequent LGD in the follow-up biopsies combined with endoscopic features.

17.
Hum Pathol ; 137: 56-62, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37127079

RESUMO

Genetic aberrations in the Estrogen Receptor 1 (ESR1) gene have been identified as an important mechanism of resistance to endocrine therapy in metastatic breast carcinoma. In this study, we aimed to correlate ESR1 genetic aberrations with the ER and PR status in paired metastatic and primary breast carcinomas. Patients with ER-positive breast cancer were divided into two groups: ESR1 genetic aberration (n = 26) and wild-type control (n = 29) based on genetic profiling of their metastatic tumors. Clinicopathological features and ER/PR status were analyzed in paired primary and metastatic tumors. Although there was no significant difference in ER expression between the ESR1 aberration and control groups in primary tumors, ER positivity rate in metastatic tumors was significantly higher in the ESR1 aberration group than in the control group (100% vs. 86%, P < .05). ESR1 aberrated cases were associated with more liver metastases than control tumors (46% vs. 10%, P < .01). The ER percentage and intensity slightly increased from primary to metastatic tumors in the ESR1 aberration group compared to a decrease in both in the wild-type group (percentage increase 2% vs. decrease 19%, P = .0594; intensity increase 0.04 vs. decrease 0.8, p < .05). Patients with ESR1 aberrated metastases were more likely than those with wild-type ESR1 metastases to have the following characteristics: 1) ER percentage ≥90% and intensity >2, as well as PR percentage ≥30% and intensity >1 in metastatic tumors; 2) ER percentage ≥90% and PR percentage ≥70% in primary tumors; and 3) slightly increase in ER percentage and intensity from primary to metastatic tumors. Based on the ER/PR parameters of paired primary and metastatic breast cancer, ESR1 aberration in metastasis may be predicted.


Assuntos
Neoplasias da Mama , Receptores de Estrogênio , Humanos , Feminino , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética
18.
Microbiol Spectr ; 11(4): e0407322, 2023 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-37358412

RESUMO

Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Humanos , Sorogrupo , Estudo de Associação Genômica Ampla , Vacinas Pneumocócicas/genética , Sorotipagem
19.
Breast ; 72: 103586, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37812963

RESUMO

BACKGROUND: Retesting for Human epidermal growth factor receptor-2 (HER2) in post-neoadjuvant therapy resection is variable, and data is conflicting regarding the prognostic significance of changes in HER2 expression pre and post therapy. METHODS: We identified 104 patients with localized HER2 IHC 3+ breast cancer who received neoadjuvant trastuzumab(T)/pertuzumab(P) containing chemotherapy at Yale Cancer Center between 2012 and 2022. Patients were divided into 3 cohorts by response and HER2 IHC in the residual disease: Cohort 1 pathologic complete response (pCR), Cohort 2 pre-treatment IHC 3+/post treatment IHC 1+/2+, and Cohort 3 pre-treatment IHC 3+/post-treatment IHC 3+. Kaplan-Meier survival analysis was performed to assess recurrence free survival at 36 months. RESULTS: The overall pCR rate was 62.5% (65/104), while 37.5% (39/104) of patients had residual disease (RD). Among patients with RD, 58.9% (23/39) remained IHC 3+ and 41.1% (16/39) had reduced HER2 expression IHC1+ or 2+. In patients with HER2 IHC 3+ RD, 26% (6/23) developed local recurrence or distant metastasis while none of patients with post NAT HER2 IHC 1+ or 2+ RD had relapse (p = 0.0309). In patients with pCR, 6.15% (4/65) had recurrence. Kaplan-Meier survival analysis revealed superior disease-free survival in patients with reduced HER2 IHC expression compared to those with remained IHC 3+ (log rank p = 0.004). CONCLUSION: We conclude that reduced HER2 expression by IHC following neoadjuvant treatment was associated with lower recurrence rates in HER2 IHC 3+ breast cancer. If confirmed, RD HER2 IHC expression could be used as a prognostic biomarker to stratify patients in adjuvant trials and identify patients who may benefit from more intensive adjuvant therapy and post therapy surveillance.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Prognóstico , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/etiologia , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêutico
20.
Arch Pathol Lab Med ; 147(11): 1298-1306, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730476

RESUMO

CONTEXT.­: Repeated surgery is necessary for 20% to 40% of breast conservation surgeries owing to the unavailability of any adjunctive, accurate, and objective tool in the surgeon's hand for real-time margin assessment to achieve the desired balance of oncologic and cosmetic outcomes. OBJECTIVE.­: To assess the feasibility of using a multispectral autofluorescence imaging device for discriminating malignant neoplasm from normal breast tissue in pathology as a critical step in the development of a device for intraoperative use, and to demonstrate the device's utility for use in processing and prioritizing specimens during frozen section and in the pathology grossing room. DESIGN.­: We performed a preliminary assessment of our device, called the TumorMAP system, on 172 fresh tissue blocks from 115 patients obtained from lumpectomy specimens at the time of initial gross examination and compared the device results with gold standard pathology evaluation. RESULTS.­: The preliminary results demonstrate the potential of our device in detecting breast cancer in fresh tissue samples with a sensitivity of 82%, a specificity of 91%, a positive predictive value of 84%, and a negative predictive value of 89%. CONCLUSIONS.­: Our results suggest that the TumorMAP system is suitable for the detection of malignant neoplasm in freshly excised breast specimens and has the potential to evaluate resection margins in real time.

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