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1.
Ann Surg Oncol ; 31(3): 2069-2077, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37996643

RESUMO

BACKGROUND OR PURPOSE: Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies. PATIENTS AND METHODS: Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples. RESULTS: There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid. CONCLUSIONS: The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.


Assuntos
Carcinoma , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Interleucina-8 , Interleucina-6 , Líquido Ascítico , Carcinoma/patologia , Imunoterapia , Microambiente Tumoral
2.
Cell Biol Int ; 48(5): 610-625, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38263584

RESUMO

Fucosyltransferases (Fut) regulate the fucosylation process associated with tumorogenesis in different cancer types. Ascitic fluid (AF) from patients diagnosed with advanced stage of epithelial ovarian cancer (EOC) is considered as a dynamic tumor microenvironment associated with poor prognosis. Previous studies from our laboratory showed increased fucosylation in SKOV-3 and OVCAR-3, cancer-derived cell lines, when these cells were incubated with AFs derived from patients diagnosed with EOC. In the present work we studied three fucosyltransferases (Fut 2, Fut 4, and Fut 8) in SKOV-3, OVCAR-3 and CAOV-3 cell lines in combination with five different AFs from patients diagnosed with this disease, confirming that all tested AFs increased fucosylation. Then, we demonstrate that mRNAs of these three enzymes were overexpressed in the three cell lines under treatment with AFs. SKOV-3 showed the higher overexpression of Fut 2, Fut 4, and Fut 8 in comparison with the control condition. We further confirmed, in the SKOV-3 cell line, by endpoint PCR, WB, and confocal microscopy, that the three enzymes were overexpressed, being Fut 4 the most overexpressed enzyme compared to Fut 2 and Fut 8. These enzymes were concentrated in vesicular structures with a homogeneous distribution pattern throughout the cytoplasm. Moreover, we found that among the three enzymes, only Fut 4 was located inside the nuclei. The nuclear location of Fut 4 was confirmed for the three cell lines. These results allow to propose Fut 2, Fut 4, and Fut 8 as potential targets for EOC treatment or as diagnostic tools for this disease.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/metabolismo , Carcinoma Epitelial do Ovário , Líquido Ascítico/metabolismo , Líquido Ascítico/patologia , Galactosídeo 2-alfa-L-Fucosiltransferase , Apoptose , Linhagem Celular Tumoral , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Microambiente Tumoral
3.
BMC Infect Dis ; 24(1): 503, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769522

RESUMO

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is an emerging technique for the clinical diagnosis of infectious disease that has rarely been used for the diagnosis of ascites infection in patients with cirrhosis. This study compared mNGS detection with conventional culture methods for the on etiological diagnosis of cirrhotic ascites and evaluated the clinical effect of mNGS. METHODS: A total of 109 patients with ascites due to cirrhosis were included in the study. We compared mNGS with conventional culture detection by analyzing the diagnostic results, pathogen species and clinical effects. The influence of mNGS on the diagnosis and management of ascites infection in patients with cirrhosis was also evaluated. RESULTS: Ascites cases were classified into three types: spontaneous bacterial peritonitis (SBP) (16/109, 14.7%), bacterascites (21/109, 19.3%) and sterile ascites (72/109, 66.1%). In addition, 109 patients were assigned to the ascites mNGS-positive group (80/109, 73.4%) or ascites mNGS-negative group (29/109, 26.6%). The percentage of positive mNGS results was significantly greater than that of traditional methods (73.4% vs. 28.4%, P < 0.001). mNGS detected 43 strains of bacteria, 9 strains of fungi and 8 strains of viruses. Fourteen bacterial strains and 3 fungal strains were detected via culture methods. Mycobacteria, viruses, and pneumocystis were detected only by the mNGS method. The mNGS assay produced a greater polymicrobial infection rate than the culture method (55% vs. 16%). Considering the polymorphonuclear neutrophil (PMN) counts, the overall percentage of pathogens detected by the two methods was comparable, with 87.5% (14/16) in the PMN ≥ 250/mm3 group and 72.0% (67/93) in the PMN < 250/mm3 group (P > 0.05). Based on the ascites PMN counts combined with the mNGS assay, 72 patients (66.1%) were diagnosed with ascitic fluid infection (AFI) (including SBP and bacterascites), whereas based on the ascites PMN counts combined with the culture assay, 37 patients (33.9%) were diagnosed with AFI (P < 0.05). In 60 (55.0%) patients, the mNGS assay produced positive clinical effects; 40 (85.7%) patients had their treatment regimen adjusted, and 48 patients were improved. The coincidence rate of the mNGS results and clinical findings was 75.0% (60/80). CONCLUSIONS: Compared with conventional culture methods, mNGS can improve the detection rate of ascites pathogens, including bacteria, viruses, and fungi, and has significant advantages in the diagnosis of rare pathogens and pathogens that are difficult to culture; moreover, mNGS may be an effective method for improving the diagnosis of ascites infection in patients with cirrhosis, guiding early antibiotic therapy, and for reducing complications related to abdominal infection. In addition, explaining mNGS results will be challenging, especially for guiding the treatment of infectious diseases.


Assuntos
Ascite , Sequenciamento de Nucleotídeos em Larga Escala , Cirrose Hepática , Metagenômica , Peritonite , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Masculino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Feminino , Pessoa de Meia-Idade , Ascite/microbiologia , Metagenômica/métodos , Peritonite/microbiologia , Peritonite/diagnóstico , Idoso , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Adulto , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Líquido Ascítico/microbiologia
4.
Clin Chem Lab Med ; 62(7): 1266-1276, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38112289

RESUMO

Ascites is the pathological accumulation of fluid within the peritoneal cavity. It often occurs as results of liver cirrhosis, malignant neoplasia, tuberculous infection, cardiac insufficiency, renal diseases, etc. Determining the etiology is an essential step in the management of patients with new-onset ascites. Abdominal paracentesis with appropriate ascitic fluid analysis is probably the most cost-effective method of determining the cause of ascites. We performed a literature search of PubMed and identified articles published in the field of ascites, to evaluate diagnostic values of various parameters in defining the etiologies of ascites and then provides diagnostic algorithm for patients with new-onset ascites. In patients with ascites, the constituent ratio of underlying etiology varies between developed and developing countries. It is a challenge to define the etiologies of ascites in developing countries. Routine ascitic fluid analysis should include the serum ascites albumin gradient (SAAG), total protein concentration, cell count and differential. Optional ascitic fluid analysis includes cholesterol, fluid culture, cytology, tumor markers, lactate dehydrogenase, adenosine deaminase (ADA), triglyceride, amylase, glucose, brain natriuretic peptide (BNP), etc. Our review evaluated diagnostic values of the above parameters in defining the etiologies of ascites. Diagnostic algorithm established in this review would provide a practical and convenient diagnostic strategy for clinicians in diagnosing patients with new-onset ascites.


Assuntos
Algoritmos , Ascite , Líquido Ascítico , Humanos , Ascite/diagnóstico , Diagnóstico Diferencial
5.
BMC Womens Health ; 24(1): 148, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424540

RESUMO

INTRODUCTION: Endometriosis (EM) is a multifactorial disease that affects 10 - 15% of women of reproductive age. Additionally, 30-50% of women with EM suffer from infertility. The mechanism of infertility caused by EM has not yet been consistently explained. In recent years, studies have shown a link between infertility associated with EM and changes in the reproductive tract microbiota. METHODS: In this study, we involved 26 EM patients (8 cases of stage I-II and 18 cases of stage III-IV) and 31 control subjects who were tubal obstruction-related infertility (TORI). The samples from peritoneal fluid (PF) and uterine fluid (UF) were collected and sequenced by 16 S rRNA amplicon. RESULTS: In the comparison of microbial diversity, we found no significant differences in the microbial diversity of PF and UF between patients with stage I-II EM and those with TORI. However, there was a significant difference in microbial diversity among patients with stage III-IV EM compared to the previous two groups. Lactobacillus decreased in PF of EM compared to the control group, while it increased in UF. In PF, the abundance of Pseudomonas, Enterococcus, Dubosiella and Klebsiella was significantly higher in patients with stage III-IV compared to TORI patients. And in UF, the main differences existed between stage I-II EM compared to the other two groups. The abundance of pontibacter, aquabacterium, Rikenellaceae and so on at the genus level was significantly enriched in the EM patients with stage I-II. In the analysis based on KEGG database, EM may affect the receptivity related pathways of the endometrium by influencing changes in the uterine microbiota. CONCLUSION: Our results indicated that as EM progresses, the microorganisms in UF and PF keep changing. These changes in the microbiota, as well as the resulting alternations in gene functional classification, may play an important role in the infertility associated with EM.


Assuntos
Endometriose , Infertilidade Feminina , Doenças Uterinas , Humanos , Feminino , Endometriose/metabolismo , Infertilidade Feminina/etiologia , Líquido Ascítico/metabolismo , Endométrio/metabolismo
6.
Langenbecks Arch Surg ; 409(1): 244, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115580

RESUMO

BACKGROUND: The distinction between complicated and uncomplicated acute appendicitis (AA) is important as it guides postoperative antibiotic treatment. A diagnosis based on intraoperative findings is imprecise and standard cultivation of peritoneal fluid is generally time-consuming with little clinical benefit. The aim of this study was to examine if cultivation of peritoneal fluid in acute appendicitis could reliably detect bacteria within 24 h. METHODS: Patients older than 18 years undergoing laparoscopic appendectomy were prospectively enrolled at two surgical departments after informed consent was obtained. Periappendicular fluid was collected prior to appendectomy and sent for cultivation. Sensitivity, specificity and positive and negative predictive values were calculated with 95% confidence intervals (CIs) using 72-hour cultivation results as the gold standard. Patients with complicated AA as determined by the surgeon, received a three-day course of oral antibiotics. Postoperative infectious complications within 30 days after surgery were registered. RESULTS: From July 2020 to January 2021, 101 patients were included. The intraoperative diagnosis was complicated AA in 34 cases. Of these patients, six (17.6%) had bacteria cultured within 24 h after surgery, leading to a sensitivity of 60% and a specificity of 100%. The positive and negative predictive values were 1.00 and 0.96, respectively. Seven patients developed a postoperative infection (five superficial wound infections and two intra-abdominal abscess). In all cases with a positive cultivation result, the intraoperative diagnosis was complicated appendicitis and a postoperative course of antibiotics prescribed. CONCLUSION: Twenty-four-hour cultivation of the peritoneal fluid in acute appendicitis is a valid indicator for peritoneal bacterial contamination. Randomized studies are necessary to determine if this approach is suitable for targeting postoperative antibiotic treatment as a means to prevent overtreatment without increasing the risk of infectious complications.


Assuntos
Apendicectomia , Apendicite , Líquido Ascítico , Humanos , Apendicite/cirurgia , Apendicite/diagnóstico , Feminino , Masculino , Estudos Prospectivos , Líquido Ascítico/microbiologia , Adulto , Pessoa de Meia-Idade , Prognóstico , Laparoscopia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Antibacterianos/uso terapêutico , Idoso , Diagnóstico Diferencial , Doença Aguda , Fatores de Tempo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Estudos de Coortes
7.
Cytopathology ; 35(1): 173-176, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37828808

RESUMO

Anorectal malignant melanomas are rare, accounting for less than 2% of all melanomas. Malignant effusions developing secondary to malignant melanoma are highly uncommon. Herein, we present the cytomorphological features of a metastatic anorectal malignant melanoma presenting with ascites at the initial clinical presentation.


Assuntos
Melanoma , Humanos , Masculino , Idoso , Melanoma/diagnóstico , Melanoma/patologia , Líquido Ascítico/patologia , Citologia , Ascite/patologia , Hemorragia Gastrointestinal/patologia
8.
Gynecol Obstet Invest ; 89(4): 335-345, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38569489

RESUMO

OBJECTIVES: Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serve as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. DESIGN: Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. PARTICIPANTS: Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. METHODS: The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. RESULTS: Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the rASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the rASRM endometriosis score. In receiver operating characteristic analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. LIMITATIONS: Some limitations of the current study deserve to be underlined. First, the sensitive ELISA method was the sole-validated tool for detecting the markers in patient samples. Second, healthy or fertile women were not involved as the control group. CONCLUSIONS: The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Biomarcadores , Endometriose , Infertilidade Feminina , Receptores de Lipopolissacarídeos , Fatores Inibidores da Migração de Macrófagos , Receptores de Superfície Celular , Humanos , Feminino , Endometriose/sangue , Endometriose/complicações , Adulto , Antígenos CD/sangue , Receptores de Superfície Celular/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores/sangue , Receptores de Lipopolissacarídeos/sangue , Oxirredutases Intramoleculares/sangue , Estudos de Casos e Controles , Estudos Prospectivos , Líquido Ascítico/química , Líquido Ascítico/metabolismo
9.
Parasitol Res ; 123(8): 293, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105851

RESUMO

Side effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.


Assuntos
Alginatos , Modelos Animais de Doenças , Nanopartículas , Toxoplasma , Toxoplasmose Animal , Animais , Alginatos/química , Camundongos , Administração Oral , Toxoplasma/efeitos dos fármacos , Toxoplasmose Animal/tratamento farmacológico , Antiprotozoários/farmacologia , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Ácido Glucurônico , Feminino , Ácidos Hexurônicos , Fígado/parasitologia , Fígado/patologia , Fígado/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/parasitologia , Líquido Ascítico/parasitologia , Carga Parasitária , Análise de Sobrevida , Interferon gama/sangue , Camundongos Endogâmicos BALB C , Resultado do Tratamento
10.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474048

RESUMO

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.


Assuntos
Infecções Bacterianas , Peritonite , Humanos , Ascite , Lipopolissacarídeos , Âmnio , Cirrose Hepática/complicações , Líquido Ascítico/microbiologia , Antibacterianos/uso terapêutico , Peritonite/tratamento farmacológico , Infecções Bacterianas/microbiologia , Proteína Forkhead Box O1
11.
Zhonghua Bing Li Xue Za Zhi ; 53(8): 830-836, 2024 Aug 08.
Artigo em Zh | MEDLINE | ID: mdl-39103265

RESUMO

Objective: To investigate the importance of cell block and immunohistochemistry in the accurate diagnosis of serous effusion. Methods: A retrospective study was conducted on 3 124 cases of serous effusion from the Department of Pathology, Beijing Hospital from 2018 to 2022, include 2 213 cases of pleural effusion, 768 cases of peritoneal effusion, 143 cases of pericardial effusion. There were 1 699 males (54.4%) and 1 425 females (45.6%), average age 69 years old. Of which 1 292 cases were prepared with cell blocks and examined with immunohistochemical stain. Results: The percentage of malignant diagnosis increased from 64.9% (839/1 292) to 84.0% (1 086/1 292) after cell block preparation, and 1 086 cases were accurately diagnosed with histological type and/or origin of primary tumor. The undetermined diagnosis of suspected malignancy decreased from 13.3% (172/1 292) to 0.1% (1/1 292) and that of atypical hyperplasia from 18.8% (243/1 292) to 0.4% (5/1 292). The negative result for malignancy rate increased from 3.0% (38/1 292) to 15.5% (200/1 292). The differences highlighted above were statistically significant (Pearson's chi-squared test=12.739, P<0.01). Conclusion: Application of immunohistochemistry based on cell block can significantly improve malignant diagnosis in serous effusion, identify tumor origin and histological type as well as decrease the uncertain diagnosis.


Assuntos
Imuno-Histoquímica , Derrame Pericárdico , Derrame Pleural , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Derrame Pericárdico/patologia , Derrame Pleural/patologia , Derrame Pleural/diagnóstico , Líquido Ascítico/patologia , Citodiagnóstico/métodos , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia , Adulto
12.
Mol Cancer ; 22(1): 178, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932736

RESUMO

BACKGROUND: Knowing the homologous recombination deficiency (HRD) status in advanced epithelial ovarian cancer (EOC) is vital for patient management. HRD is determined by BRCA1/BRCA2 pathogenic variants or genomic instability. However, tumor DNA analysis is inconclusive in 15-19% of cases. Peritoneal fluid, available in > 95% of advanced EOC cases, could serve as an alternative source of cell-free tumor DNA (cftDNA) for HRD testing. Limited data show the feasibility of cancer panel gene testing on ascites cfDNA but no study, to date, has investigated HRD testing. METHODS: We collected ascites/peritoneal washings from 53 EOC patients (19 from retrospective cohort and 34 from prospective cohort) and performed a Cancer Gene Panel (CGP) using NGS for TP53/HR genes and shallow Whole Genome Sequencing (sWGS) for genomic instability on cfDNA. RESULTS: cfDNA was detectable in 49 out of 53 patients (92.5%), including those with limited peritoneal fluid. Median cfDNA was 3700 ng/ml, with a turnaround time of 21 days. TP53 pathogenic variants were detected in 86% (42/49) of patients, all with HGSOC. BRCA1 and BRCA2 pathogenic variants were found in 14% (7/49) and 10% (5/49) of cases, respectively. Peritoneal cftDNA showed high sensitivity (97%), specificity (83%), and concordance (95%) with tumor-based TP53 variant detection. NGS CGP on cftDNA identified BRCA2 pathogenic variants in one case where tumor-based testing failed. sWGS on cftDNA provided informative results even when tumor-based genomic instability testing failed. CONCLUSION: Profiling cftDNA from peritoneal fluid is feasible, providing a significant amount of tumor DNA. This fast and reliable approach enables HRD testing, including BRCA1/2 mutations and genomic instability assessment. HRD testing on cfDNA from peritoneal fluid should be offered to all primary laparoscopy patients.


Assuntos
DNA Tumoral Circulante , Neoplasias Ovarianas , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação , Neoplasias Ovarianas/genética , Recombinação Homóloga , Líquido Ascítico/patologia , Ascite , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma Epitelial do Ovário , Instabilidade Genômica
13.
Antimicrob Agents Chemother ; 67(5): e0172122, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37022169

RESUMO

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.


Assuntos
Líquido Ascítico , Estado Terminal , Humanos , Voriconazol/farmacocinética , Estudos Prospectivos , Antifúngicos/farmacocinética , Candida glabrata , Testes de Sensibilidade Microbiana
14.
Liver Transpl ; 29(4): 356-364, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36691984

RESUMO

Spontaneous bacterial peritonitis (SBP) is a well-recognized clinical entity with a poor prognosis. In comparison, the prevalence, microbiological flora, and prognostic significance of bacterascites (BA) (the presence of organism on culture but ascitic PMN <250 cells/mm³) is largely unknown. We, therefore, assessed the prognosis and predictors of outcome in patients with BA in comparison with those with SBP. Ascitic fluid cultures from consecutive patients with cirrhosis from 2008 to 2018 were reviewed retrospectively, and patients with SBP and BA were identified. Baseline demographic, laboratory, and microbiological data were collated and analyzed as prognostic indicators, and clinical outcomes were recorded. Patients were censored at the time of LT, death, or last follow-up. For this study 176 and 213 cases of SBP and BA, respectively, were identified and included. Patients with SBP had significantly higher Model for End-Stage Liver Disease (MELD) ( p =<0.01), peripheral blood WCC ( p < 0.01), and higher rates of Enterobacteriaceae ( p < 0.01) and multi-drug resistant pathogens ( p < 0.01). Survival at 1 and 3 months was lower in patients with SBP ( p < 0.01) when compared with BA but at 6 months and beyond, no significant difference remained. After the exclusion of deaths within 30 days of presentation, survival between SBP and BA was equivocal at all time points. Mortality was substantially higher across all MELD groupings for both SBP and BA when compared with the predicted mortality calculated by the MELD score alone. BA has a negative impact on patient survival above that predicted by the MELD score. It has similar impact to SBP on patient survival beyond 1 month suggesting it should be seen as a poor prognostic marker and prompt consideration of LT where appropriate. Further studies evaluating the role of secondary prophylaxis in this group are required.


Assuntos
Infecções Bacterianas , Doença Hepática Terminal , Transplante de Fígado , Peritonite , Humanos , Ascite/etiologia , Líquido Ascítico , Estudos Retrospectivos , Doença Hepática Terminal/complicações , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Prognóstico , Peritonite/diagnóstico , Peritonite/epidemiologia , Peritonite/etiologia , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia
15.
Hum Reprod ; 38(4): 629-643, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36749097

RESUMO

STUDY QUESTION: Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER: This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY: Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION: A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE: We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS: Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Doenças Autoimunes , DNA Glicosilases , Endometriose , Humanos , Feminino , Endometriose/patologia , Líquido Ascítico/metabolismo , Autoanticorpos , Estudos Transversais , Proteoma/metabolismo , Proteômica , Biomarcadores , Doenças Autoimunes/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , DNA Glicosilases/metabolismo
16.
Cytokine ; 161: 156073, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326535

RESUMO

BACKGROUND: Interleukin-6 (IL-6) has been implicated in various malignancies, including ovarian cancer. However, mixed results have been observed regarding IL-6 levels in different ovarian conditions. This meta-analysis was performed to determine IL-6 levels in the peritoneal fluid and peripheral blood among patients with various adnexal masses. METHODS: Most popular English databases were searched using a predefined search formula. All studies comparing IL-6 levels in plasma, serum or peritoneal fluid of patients with benign tumors, ovarian neoplasms, and healthy controls were included based on inclusion and exclusion criteria. RESULTS: 5953 patients from 22 primary publications raging from 1994 to 2021 were included in the meta-analyses. A pooled IL-6 Mean Difference (MD) of 41 pg/mL for malignant tumors compared to benign ones, with a Confidence Interval (CI) between 19.8 and 62.2, a Z-score of 3.79, and statistical significance with a p = 0.0002 was observed. Pooled results for healthy versus benign ovarian conditions showed an MD of 5.45 pg/mL for serum or plasma IL-6 measurements in favor of benign tumors (CI:0.66-10.25, Z = 2.23 and p = 0.03). The analysis showed an MD for IL-6 levels of 19.59 pg/mL for healthy controls versus malignant ovarian tumors. Peritoneal fluid measurements regarding IL-6's levels showed no significant difference between benign or malignant masses. DISCUSSION/CONCLUSIONS: Higher levels of plasma or serum IL-6 in ovarian neoplasia patients compared to benign conditions or healthy controls identify IL-6 as a discerning factor between benign or malignant ovarian tumors and a potential biomarker for ovarian malignancy.


Assuntos
Interleucina-6 , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/patologia , Líquido Ascítico/química , Líquido Ascítico/patologia , Biomarcadores
17.
BMC Gastroenterol ; 23(1): 272, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559036

RESUMO

BACKGROUND: Recently, a simple scoring system named the Mansoura scoring system was developed to predict spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. However, the efficacy of this newly developed system has not been extensively investigated. We aimed to validate a new simple scoring system for the rapid diagnosis or exclusion of SBP without paracentesis. METHODS: Adult patients with cirrhosis and ascites admitted to Cho Ray Hospital between November 2021 and May 2022 were included. The area under the receiver operating characteristic (AUROC) curve of the Mansoura simple scoring system for predicting SBP was calculated using the Stata software. Other independent laboratory tests for predicting SBP (C-reactive protein [CRP], neutrophil-to-lymphocyte ratio [NLR], and mean platelet volume [MPV]) were assessed and compared using the Mansoura scoring system. RESULTS: A total of 121 patients were included in this study. The Mansoura scoring system showed good performance in predicting SBP in patients with cirrhosis and ascites (AUROC:0.89). At the cut-off ≥ 4 points, the scoring system achieved a specificity of 97.7% with a positive predictive value for the diagnosis of SBP of 93.5%. Multivariate analysis was performed using our data and showed that NLR, CRP level, and MPV were independent factors related to SBP. CONCLUSION: The Mansoura scoring system demonstrated good performance in predicting SBP in patients with cirrhosis and ascites and may help guide management decisions.


Assuntos
Infecções Bacterianas , Peritonite , Adulto , Humanos , Ascite/microbiologia , Peritonite/complicações , Peritonite/diagnóstico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Proteína C-Reativa/metabolismo , Neutrófilos , Infecções Bacterianas/complicações , Infecções Bacterianas/diagnóstico , Líquido Ascítico/metabolismo
18.
BMC Infect Dis ; 23(1): 84, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750816

RESUMO

BACKGROUND: Mycobacterium aubagnense, which was first characterized in 2006, is a non-tuberculosis mycobacterium (NTM) that has only been isolated from respiratory secretions and joint fluid. With only four cases globally, the microbe has rarely been reported in human clinical cases and the strain has not been isolated from ascites. CASE PRESENTATION: To the best of our knowledge, this is the first time that M. aubagnense has been isolated from ascites samples of a patient with severe peritoneal effusion and normal liver functions. Anti-NTM therapy with moxifloxacin, ethambutol, and isoniazid combined with furosemide and spironolactone diuretic therapy relieved the symptoms after six months. CONCLUSIONS: Increased puncture and drainage of ascites combined with diuretic treatment did not significantly relieve the ascites, leading to relapse with aggravated symptoms. The subsequent anti-NTM treatment with moxifloxacin, ethambutol, and isoniazid alleviated the degree of ascites. Therefore, we postulated that M. aubagnense infection was the potential cause of the difficult reduction of ascites in this patient. However, the ascites repeatedly occurred in the patient, which was attributed to M. aubagnense resistance due to insufficient medication time and repeated medication. The patient's underlying diseases may also result in ascites. Therefore, there is a need for careful analysis of the clinical significance of M. aubagnense.


Assuntos
Etambutol , Infecções por Mycobacterium não Tuberculosas , Humanos , Etambutol/uso terapêutico , Isoniazida/uso terapêutico , Moxifloxacina/uso terapêutico , Líquido Ascítico , Ascite/tratamento farmacológico , Micobactérias não Tuberculosas , Diuréticos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/microbiologia
19.
Dig Dis Sci ; 68(5): 2140-2148, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36879176

RESUMO

BACKGROUND AND AIMS: Cirrhotic patients presenting with spontaneous bacterial peritonitis (SBP) have elevated risk of short-term mortality. While high Model for End-Stage Liver Disease-Sodium score (MELD-Na) and ascites culture yielding multi-drug resistance (MDR) bacteria are well established risk factors for further aggravating mortality, the impact of individual, causative microorganisms and their respective pathogenesis have not been previously investigated. METHODS: This is a retrospective study of 267 cirrhotic patients at two tertiary care hospitals undergoing paracentesis from January 2015 to January 2021 who presented with ascitic PMN count > 250 cells/mm3. The primary outcome was SBP progression defined as death or liver transplantation within 1-month of paracentesis stratified by microorganism type. RESULTS: Of 267 patients with SBP, the ascitic culture yielded causative microorganism in 88 cases [median age 57 years (IQR 52-64)]; 68% male; median MELD-Na 29 (IQR 23-35). The microbes isolated were E. coli (33%), Streptococcus (15%), Klebsiella (13%), Enterococcus (13%), Staphylococcus (9%) and others (18%); 41% were MDR. Cumulative incidence of SBP progression within 1-month was 91% (95% CI 67-100) for Klebsiella, 59% (95% CI 42-76) for E. coli, and 16% (95% CI 4-51) for Streptococcus. After adjusting for MELD-Na and MDR, risk of SBP progression remained elevated for Klebsiella (HR 2.07; 95% CI 0.98-4.24; p-value = 0.06) and decreased for Streptococcus (HR 0.28; 95% CI 0.06-1.21; p-value = 0.09) compared to all other bacteria. CONCLUSION: Our study found Klebsiella-associated SBP had worse clinical outcomes while Streptococcus-associated SBP had the most favorable outcomes after accounting for MDR and MELD-Na. Thus, identification of the causative microorganism is crucial not only for optimizing the treatment but for prognostication.


Assuntos
Infecções Bacterianas , Doença Hepática Terminal , Peritonite , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Doença Hepática Terminal/complicações , Escherichia coli , Índice de Gravidade de Doença , Peritonite/diagnóstico , Peritonite/tratamento farmacológico , Ascite/etiologia , Infecções Bacterianas/complicações , Líquido Ascítico
20.
J Infect Chemother ; 29(3): 309-315, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36549644

RESUMO

INTRODUCTION: Cefmetazole (CMZ) has gained interest as a carbapenem-sparing alternative to the epidemic of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-E). In this study, we investigated the pharmacokinetics (PK) of CMZ in plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue to assess the dosing regimen needed to achieve pharmacodynamic (PD) goals at the target site. METHODS: Patients scheduled for elective lower gastrointestinal surgery were intravenously administered CMZ. Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected after CMZ infusion and during the surgery, and CMZ concentrations were measured. The non-compartmental and compartmental PK parameters were estimated and used to evaluate site-specific PD target attainment. RESULTS: A total of 38 plasma, 27 peritoneal fluid, 36 peritoneum, and 38 subcutaneous adipose tissue samples were collected from 10 patients. The non-compartmental PK analysis revealed the ratios of the mean area under the drug concentration-time curve (AUC0-3.5 h) of peritoneal fluid-to-plasma, peritoneum-to-plasma, and subcutaneous adipose tissue-to-plasma were 0.60, 0.36, and 0.11, respectively. The site-specific PD target attainment analyses based on the breakpoints for ESBL-E per the Japanese surgical site infection (SSI) surveillance (MIC90 = 8 mg/L) revealed that 2 g CMZ every 3.5 h achieved desired bactericidal effect at all sites and 2 g CMZ every 6 h achieved PD goals at peritoneum and peritoneal fluid. CONCLUSION: These findings clarify the PK of CMZ in abdominal tissues and could help decide optimal dosing regimens to treat intra-abdominal infection and prophylaxis of SSI.


Assuntos
Cefmetazol , Procedimentos Cirúrgicos do Sistema Digestório , Humanos , Cefmetazol/uso terapêutico , Peritônio , Líquido Ascítico , Antibacterianos/farmacologia , Gordura Subcutânea , Testes de Sensibilidade Microbiana
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