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1.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064637

RESUMO

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs-besides being important regulators of cancer development-may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein-protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.


Assuntos
Biomarcadores Tumorais/genética , MicroRNA Circulante/genética , Redes Reguladoras de Genes , Glioblastoma/genética , Glioblastoma/patologia , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , MicroRNA Circulante/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Glioblastoma/sangue , Humanos , Prognóstico , Mapas de Interação de Proteínas
2.
BMC Infect Dis ; 21(1): 514, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074256

RESUMO

BACKGROUND: Talaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years. METHODS: From January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-ß-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was < 0.05. RESULTS: A total of 87 patients were collected, with a median age of 34 years, a median hemoglobin of 94 g/L and CD4 count of 7/µl. The rate of TM bloodstream infection among all in-hospital patients increased from 0.99% in 2015 to 2.09% in 2020(half year). Patients with TM bloodstream infection with CD8 count < 200/µl had a 12.6-fold higher risk of poor prognosis than those with CD8 count > 200/µl (p = 0.04), and those with BDG < 100 pg/mL had a 34.9-fold higher risk of poor prognosis than those with BDG > 100 pg/mL (p = 0.01). CONCLUSIONS: TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/µl is with an increased risk of poor prognosis.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Fungemia/epidemiologia , Micoses/epidemiologia , Talaromyces/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , China/epidemiologia , Feminino , Fungemia/diagnóstico , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco
3.
Crit Care ; 25(1): 186, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074313

RESUMO

BACKGROUND: In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. METHODS: Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. RESULTS: Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14-21) vs. 15 (11-19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18-27) vs. 21 (15-24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70-109) vs. 100 (80-124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. CONCLUSION: Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov (NCT04337983). Registered 30 March 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .


Assuntos
COVID-19/metabolismo , Permeabilidade Capilar , Água Extravascular Pulmonar/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Índice de Gravidade de Doença , COVID-19/complicações , Hemodinâmica , Humanos , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Prognóstico , Edema Pulmonar/metabolismo , Termodiluição
4.
World J Surg Oncol ; 19(1): 161, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082777

RESUMO

BACKGROUND: Breast cancer (BC) is the most commonly malignant tumor among women worldwide. Many studies have reported that circular RNAs (circRNAs) were participated in the regulation of multiple cancers development. However, the mechanism underlying hsa_circ_0001982 in breast cancer development is still unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001982, microRNA-1287-5p (miR-1287-5p), and mucin 19 (MUC19) in BC tissues and cells under hypoxia. Moreover, glycolysis was evaluated by glucose consumption, lactic acid production, and hexokinase II (HK2) protein levels. The protein levels of cyclin D1, proliferating cell nuclear antigen (PCNA), and HK2 were determined by western blot assay. Cell proliferation, migration, and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) and transwell assays, respectively. The relationship between miR-1287-5p and circ_0001982 or MUC19 was predicted using starbase v3.0 or Targetscan, and verified by dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. The xenograft model in nude mice was established to examine the effect of circ_0001982 in vivo. RESULTS: The levels of circ_0001982 and MUC19 were upregulated, while miR-1287-5p was downregulated in BC tissues and cells under hypoxia. Knockdown of circ_0001982 hindered glycolysis, cell viability, migration, and invasion of BC cells under hypoxia. Mechanistic studies discovered that circ_0001982 could act as a sponge for miR-1287-5p to enhance MUC19 expression in BC cells. In addition, circ_0001982 silencing reduced xenograft tumor growth by regulating miR-1287-5p/MUC19 axis. CONCLUSION: Circ_0001982 affected BC cells glycolysis, proliferation, migration, and invasion through miR-1287-5p/MUC19 axis under hypoxia.


Assuntos
Neoplasias da Mama/genética , Hipóxia , MicroRNAs , Mucinas/genética , RNA Circular/genética , Animais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Transplante de Neoplasias , Prognóstico
5.
Epidemiol Psychiatr Sci ; 30: e42, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085616

RESUMO

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.


Assuntos
Antidepressivos , Depressão , Adulto , Antidepressivos/uso terapêutico , Ansiedade , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Civil , Prognóstico
6.
BMC Gastroenterol ; 21(1): 248, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34090347

RESUMO

BACKGROUND: Signet ring cell carcinoma (SRC) is a rare histological subtype of gallbladder adenocarcinoma. The current study evaluates the clinicopathologic features and prognosis of SRC. METHODS: Patients with adenocarcinoma of the gallbladder were identified in the Surveillance, Epidemiology, and End Results database from 1973 to 2016. Overall survival (OS) and cancer-specific survival (CSS) of patients who had SRC were compared with those of patients who had non-SRC using Cox regression and propensity score methods. RESULTS: Of 22,781 gallbladder adenocarcinomas retrieved, 377 (1.7%) were SRC and the other 22,404 were non-SRC. SRC was more significantly associated with older age, female gender, poor differentiation, advanced tumor stage, lymph node metastasis, distant metastasis, and advanced AJCC stage. The 5-year OS and CSS in the SRC group were 7.2 and 6.5%, respectively, both of which were significantly worse than the 13.2 and 13.3% seen in the SRC group (P = 0.002 and P = 0.012, respectively). This survival disadvantage persisted in multivariable analyses [hazard ratio (HR) = 1.256, P = 0.021 and HR = 1.211, P = 0.036] and after propensity score matching (OS: HR = 1.341, P = 0.012 and CSS: HR = 1.625, P = 0.005). Surgery in combination with chemotherapy improved OS of gallbladder SRC patients compared with surgery alone (HR = 0.726, P = 0.036) or chemotherapy alone (HR = 0.433, P < 0.001). CONCLUSION: Patients with SRC of the gallbladder have distinct clinicopathological features with poor prognosis. Surgery in combination with chemotherapy can improve survival.


Assuntos
Carcinoma de Células em Anel de Sinete , Neoplasias Gástricas , Idoso , Carcinoma de Células em Anel de Sinete/cirurgia , Feminino , Vesícula Biliar , Humanos , Prognóstico , Estudos Retrospectivos
7.
World J Surg Oncol ; 19(1): 164, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090452

RESUMO

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has recently emerged as a viable management option for peritoneal surface malignancy (PSM). CRS and HIPEC is a complex, multidisciplinary and resource-intensive surgical procedure. It has a steep learning curve and is associated with significant morbidity and mortality. The expertise is mostly limited to few dedicated high-volume centers located in developed countries. We present a single institutional experience of 232 cases of CRS and HIPEC performed at a tertiary care cancer center in a low- and middle-income country (LMIC). METHODS: A multidisciplinary PSM program was initiated in 2015 at a high-volume public-sector tertiary care cancer center in North India catering largely to patients belonging to low- and middle-income groups. Perioperative protocols were developed, and a prospective structured database was created to capture data. All patients undergoing CRS and HIPEC between January 2015 and December 2020 were identified, and the data was retrospectively analyzed for clinical spectrum, surgical details, and perioperative morbidity and mortality. RESULTS: Two hundred and thirty-two patients underwent CRS and HIPEC during the study period. Epithelial ovarian carcinoma (56.5%) was the most common malignancy treated, followed by pseudomyxoma peritonei (18.5%), colorectal carcinoma (13.4%), and malignant mesothelioma (5.6%). Optimal CRS could be achieved in 94.4% of patients. Cisplatin and mitomycin were the most common drugs used for HIPEC. A total of 28.0% of patients had morbidity including deep vein thrombosis, subacute intestinal obstruction, sepsis, burst abdomen, lymphocele, urinoma, acute renal failure, and enterocutaneous fistula. The overall treatment-related mortality was 3.5%. CONCLUSIONS: Results of the current study indicate that it is feasible to establish a successful CRS and HIPEC program for PSM in government-funded hospitals in LMIC facing resource constraints. The most common indication for CRS and HIPEC were carcinoma of the ovary followed by pseudomyxoma peritonei and colorectal carcinoma. Overall morbidity and mortality in the current series are comparable to global standards, reported from high-income countries. A protocol-based multidisciplinary team approach, optimal patient selection, and surgical expertise can help achieve optimal outcomes in government-funded hospitals in LMIC.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Procedimentos Cirúrgicos de Citorredução , Países em Desenvolvimento , Estudos de Viabilidade , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Índia/epidemiologia , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
8.
World J Surg Oncol ; 19(1): 165, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090463

RESUMO

BACKGROUND: X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. METHODS: RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. RESULTS: The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. CONCLUSION: XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Proteínas Reguladoras de Apoptose , Carcinoma Epitelial do Ovário , Feminino , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Prognóstico , RNA Longo não Codificante/genética
9.
World J Surg Oncol ; 19(1): 162, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090476

RESUMO

BACKGROUND: Pituitary adenomas are one type of intracranial tumor, which can be divided into microadenoma (≤ 1 cm), macroadenoma (> 1 cm), and giant adenoma (≥ 4 cm) according to their diametral sizes. They are benign, typically slow-progressing, whereas the biological behavior of some of them is invasive, which presents a major clinical challenge. Treatment of some pituitary adenomas is still difficult due to drug resistance or multiple relapses, usually after surgery, medication, and radiation. At present, no clear prediction and treatment biomarkers have been found in pituitary adenomas and some of them do not cause clinical symptoms, so patients are often found to be ill through physical examination, and some are even found through autopsy. With the development of research on pituitary adenomas, the immune response has become a hot spot and may serve as a novel disease marker and therapeutic target. The distribution and function of immune cells and their secreted molecules in pituitary adenomas are extremely complex. Researchers found that infiltration of immune cells may have a positive effect on the treatment and prognosis of pituitary adenomas. In this review, we summarized the advance of tumor immunity in pituitary adenomas, revealing the immunity molecules as potential biomarkers as well as therapeutic agents for pituitary adenomas. CONCLUSION: The immune studies related to pituitary adenomas may help us find relevant immune markers. At the same time, the exploration of immunotherapy also provides new options for the treatment of pituitary adenomas.


Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/terapia , Humanos , Imunoterapia , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/terapia , Prognóstico
10.
World J Surg Oncol ; 19(1): 163, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090483

RESUMO

BACKGROUND: The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. METHODS: The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. RESULTS: Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. CONCLUSION: LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.


Assuntos
Neoplasias da Vesícula Biliar , MicroRNAs , RNA Longo não Codificante , Carcinógenos , Linhagem Celular Tumoral , China , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética
11.
Zhonghua Yi Xue Za Zhi ; 101(21): 1572-1582, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34098684

RESUMO

Objective: To explore the risk factors for carbapenem-resistant Enterobacterales (CRE) infection and death. Methods: A case-control analysis of 482 inpatients in 18 secondary or tertiary hospitals in Beijing in 2018 was conducted. Patients infected by CRE were selected as the case group (n=247), and infected by carbapenem susceptible Enterobacterales (CSE) as the control group (n=235). The risk factors and clinical prognosis of CRE infection were analyzed by single factor analysis and multivariate logistic regression analysis. Results: CRE were resistant to most antimicrobials, but were highly sensitive to colistin and tigecycline, with sensitivity of 94.0% and 99.5%, respectively. Multivariate analysis showed that prior 30-day tracheal intubation (OR=2.607, 95%CI: 1.655-4.108, P<0.001), empirical treatment using third or fourth generation cephalosporins (OR=2.339, 95%CI: 1.438-3.803, P=0.001), carbapenems (OR=2.468, 95%CI: 1.610-3.782, P<0.001) and quinolones (OR=2.042, 95%CI: 1.268-3.289, P=0.003) were independent risk factors for CRE infection. Mechanical ventilation (OR=3.390, 95%CI: 1.454-7.904, P=0.005), heart failure (OR=4.679, 95%CI: 1.975-11.083, P<0.001), moderate or severe liver disease (OR=3.057, 95%CI: 1.061-8.806, P=0.038), prior 30-day quinolones exposure (OR=2.882, 95%CI: 1.241-6.691, P=0.014) and septic shock (OR=7.772, 95%CI: 3.505-17.233, P<0.001) were independent risk factors for death after CRE infection. Conclusions: Reducing the use of antimicrobials and invasive procedures such as prior 30-day tracheal intubation may reduce the probability of CRE infection. Grading the severity of the underlying disease in patients with CRE infection, as well as predicting and preventing the occurrence of septic shock will help reduce the risk of death.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecção Hospitalar , Infecções por Enterobacteriaceae , Antibacterianos/uso terapêutico , Carbapenêmicos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Prognóstico , Fatores de Risco
13.
Genes (Basel) ; 12(6)2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071309

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.


Assuntos
COVID-19/genética , COVID-19/virologia , Receptor com Domínio Discoidina 1/genética , Predisposição Genética para Doença , Interferons/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/fisiologia , Metaloproteases Semelhantes a Toloide/genética , Alelos , Biomarcadores , COVID-19/diagnóstico , COVID-19/imunologia , Estudos de Casos e Controles , Comorbidade , Citocinas/metabolismo , Feminino , Genótipo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Masculino , Prognóstico , Índice de Gravidade de Doença , Carga Viral
14.
Sci Rep ; 11(1): 11524, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075155

RESUMO

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.


Assuntos
COVID-19/complicações , Água Extravascular Pulmonar/imunologia , Edema Pulmonar/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/mortalidade , Permeabilidade Capilar , Progressão da Doença , Água Extravascular Pulmonar/virologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Prognóstico , Edema Pulmonar/diagnóstico , Edema Pulmonar/imunologia , Edema Pulmonar/virologia , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Medição de Risco/métodos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Termodiluição/métodos , Termodiluição/estatística & dados numéricos , Adulto Jovem
15.
World J Gastroenterol ; 27(20): 2615-2629, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34092979

RESUMO

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis with high mortality, which necessitates accurate clinical decision. However, studies on prognostic factors and scoring systems to predict overall survival of HRS are not enough. Meanwhile, a multicenter cohort study with a long span of time could be more convincing. AIM: To develop a novel and effective prognostic model for patients with HRS and clarify new prognostic factors. METHODS: We retrospectively enrolled 1667 patients from four hospitals, and 371 eligible patients were finally analyzed to develop and validate a novel prognostic model for patients with HRS. Characteristics were compared between survivors and non-survivors, and potential prognostic factors were selected according to the impact on 28-d mortality. Accuracy in predicting 28-d mortality was compared between the novel and other scoring systems, including Model for End-Stage Liver Disease (MELD), Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and Chinese Group on the Study of Severe Hepatitis B-Acute-on-Chronic Liver Failure (COSSH-ACLF). RESULTS: Five prognostic factors, comprised of gender, international normalized ratio, mean corpuscular hemoglobin concentration, neutrophil percentage, and stage, were integrated into a new score, GIMNS; stage is a binary variable defined by the number of failed organs. GIMNS was positively correlated with MELD, CLIF-SOFA, and COSSH-ACLF. Additionally, it had better accuracy [area under the receiver operating characteristic curve (AUROC): 0.830] than MELD (AUROC: 0.759), CLIF-SOFA (AUROC: 0.767), and COSSH-ACLF (AUROC: 0.759) in the derivation cohort (P < 0.05). It performed better than MELD and CLIF-SOFA in the validation cohort (P < 0.050) and had a higher AUROC than COSSH-ACLF (P = 0.122). CONCLUSION: We have developed a new scoring system, GIMNS, to predict 28-d mortality of HRS patients. Mean corpuscular hemoglobin concentration and stage were first proposed and found to be related to the mortality of HRS. Additionally, the GIMNS score showed better accuracy than MELD and CLIF-SOFA, and the AUROC was higher than that of COSSH-ACLF.


Assuntos
Doença Hepática Terminal , Síndrome Hepatorrenal , Estudos de Coortes , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/etiologia , Humanos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
Infez Med ; 29(2): 224-228, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061787

RESUMO

Vitamin D deficiency has been associated to respiratory tract infections. We aimed to investigate vitamin D plasma levels in patients with chest infection with and without COVID-19 in a hospitalized population during the second pandemic wave. A prospective study was conducted in a Mediterranean tertiary center referring to 80 patients suffering from chest infection, who were divided into two groups according to a positive test for SARS-CoV-2 infection. The hospitalized COVID-19 patients had a high prevalence of vitamin D deficiency, and these patients also exhibited higher levels of plasma inflammatory markers. Intensive research is required to identify the role and mechanisms of vitamin D in patients with SARSCoV-2 infection and its possible role as a prognostic factor of the disease.


Assuntos
COVID-19/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , Idoso , Feminino , Grécia/epidemiologia , Humanos , Mediadores da Inflamação/sangue , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Centros de Atenção Terciária , Deficiência de Vitamina D/sangue
17.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068143

RESUMO

Immune checkpoint inhibitor (ICI) therapies have shown great promise in cancer treatment. However, the intra-heterogeneity is a major barrier to reasonably classifying the potential benefited patients. Comprehensive heterogeneity analysis is needed to solve these clinical issues. In this study, the samples from pan-cancer and independent breast cancer datasets were divided into four tumor immune microenvironment (TIME) subtypes based on tumor programmed death ligand 1 (PD-L1) expression level and tumor-infiltrating lymphocyte (TIL) state. As the combination of the TIL Z score and PD-L1 expression showed superior prediction of response to ICI in multiple data sets compared to other methods, we used the TIL Z score and PD-L1 to classify samples. Therefore, samples were divided by combined TIL Z score and PD-L1 to identify four TIME subtypes, including type I (3.24%), type II (43.24%), type III (6.76%), and type IV (46.76%). Type I was associated with favorable prognosis with more T and DC cells, while type III had the poorest condition and composed a higher level of activated mast cells. Furthermore, TIME subtypes exhibited a distinct genetic and transcriptional feature: type III was observed to have the highest mutation rate (77.92%), while co-mutations patterns were characteristic in type I, and the PD-L1 positive subgroup showed higher carbohydrates, lipids, and xenobiotics metabolism compared to others. Overall, we developed a robust method to classify TIME and analyze the divergence of prognosis, immune cell composition, genomics, and transcriptomics patterns among TIME subtypes, which potentially provides insight for classification of TIME and a referrable theoretical basis for the screening benefited groups in the ICI immunotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Regulação Neoplásica da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Microambiente Tumoral/imunologia , Feminino , Seguimentos , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Taxa de Sobrevida
18.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068442

RESUMO

Advanced glycation end products (AGEs) are produced in response to a high-glucose environment and oxidative stress and exacerbate various diseases. Nε-(Carboxymethyl)lysine (CML) is an AGE that is produced by the glycation of lysine residues of proteins. There are a few reports on alterations in protein function due to CML modification; however, its association with cancer is not clear. We investigated the significance of CML modification in high mobility group box protein-1 (HMGB1), a cytokine that is significantly associated with cancer progression. Treatment of the gastric cancer cell lines TMK1 and MKN74 with glyoxal or glucose resulted in increased CML modification compared to untreated cells. CML-HMGB1 was modified via oxidation and more pronouncedly activated the receptor for AGE and downstream AKT and NF-κB compared to naïve HMGB1 and oxidized HMGB1. CML-HMGB1 bound with reduced affinity to DNA and histone H3, resulting in enhanced extranuclear translocation and extracellular secretion. Treatment of gastric cancer cells with CML-HMGB1 enhanced cell proliferation and invasion, sphere formation, and protection from thapsigargin-induced apoptosis, and decreased 5-FU sensitivity in comparison to HMGB1. Further, CML-HMGB1 was detected at various levels in all the 10 gastric cancer tumor specimens. HMGB1 levels correlated with primary tumor progression and distant metastasis, whereas CML-HMGB1 levels were associated with primary tumor progression, lymph node metastasis, distant metastasis, and stage. In addition, CML-HMGB1 levels correlated with oxidative stress in cancer tissues and resistance to neoadjuvant therapy. Therefore, CML modification of HMGB1 enhanced the cancer-promoting effect of HMGB1. In this study, CML-HMGB1 has been highlighted as a new therapeutic target, and analysis of the molecular structure of CML-HMGB1 is desired in the future.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Produtos Finais de Glicação Avançada/metabolismo , Proteína HMGB1/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Glicosilação , Proteína HMGB1/genética , Humanos , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas
20.
BMC Pediatr ; 21(1): 260, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088294

RESUMO

BACKGROUND: For evidence-based decision making, primary care physicians need to have specific and reliable information on the pre-test probabilities of underlying diseases and a symptom's course. We performed a systematic review of symptom-evaluating studies in primary care, following three research questions: (1) What is the prevalence of the symptom cough in children consulting primary care physicians? (2) What are the underlying aetiologies of cough and the respective frequencies? (3) What is the prognosis of children with cough? METHODS: Following a pre-defined algorithm and independent double reviewer ratings we searched MEDLINE and EMBASE. All quantitative original research articles in English, French or German were included if they focused on unselected study populations of children consulting a primary care physician for cough. We used the random effects model for meta-analysis in subgroups, if justifiable in terms of heterogeneity. RESULTS: We identified 14 eligible studies on prevalence, five on aetiology and one on prognosis. Prevalence estimates varied between 4.7 and 23.3% of all reasons for an encounter, or up to estimates of 60% when related to patients or consultations. Cough in children is more frequent than in adults, with lowest prevalences in adolescents and in summer. Acute cough is mostly caused by upper respiratory tract infections (62.4%) and bronchitis (33.3%); subacute or chronic cough by recurrent respiratory tract infection (27.7%), asthma (up to 50.4% in cough persisting more than 3 weeks), and pertussis (37.2%). Potentially serious diseases like croup, pneumonia or tuberculosis are scarce. In children with subacute and chronic cough the total duration of cough ranged from 24 to 192 days. About 62.3% of children suffering from prolonged cough are still coughing two months after the beginning of symptoms. CONCLUSION: Cough is one of the most frequent reasons for an encounter in primary care. Our findings fit in with current guideline recommendations supporting a thoughtful wait-and-see approach in acute cough and a special awareness in chronic cough of the possibility of asthma and pertussis. Further evidence of aetiological pre-test probabilities is needed to assess the diagnostic gain based on patient history and clinical signs for differential diagnoses of cough in children.


Assuntos
Tosse , Medicina de Família e Comunidade , Adolescente , Adulto , Criança , Tosse/diagnóstico , Tosse/epidemiologia , Tosse/etiologia , Humanos , Prevalência , Atenção Primária à Saúde , Prognóstico
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