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1.
Gene ; 806: 145935, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34478821

RESUMEN

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Asunto(s)
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiones no Traducidas 3' , Adulto , Anciano , Antígeno B7-H1/sangre , Biomarcadores/sangre , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Virus de la Hepatitis B/crecimiento & desarrollo , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/virología , Humanos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
2.
J Med Virol ; 94(1): 222-228, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34449894

RESUMEN

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.


Asunto(s)
COVID-19/virología , Proteínas de la Nucleocápside de Coronavirus/sangre , Enfermedad Crítica , SARS-CoV-2 , Adulto , Anciano , Anciano de 80 o más Años , Antígenos Virales/sangre , Biomarcadores/análisis , Biomarcadores/sangre , COVID-19/mortalidad , Proteínas de la Nucleocápside de Coronavirus/inmunología , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Fosfoproteínas/sangre , Fosfoproteínas/inmunología , Estudios Prospectivos , ARN Viral/análisis , ARN Viral/sangre , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Tráquea/virología , Adulto Joven
3.
J Med Virol ; 94(1): 384-387, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34406670

RESUMEN

The antiviral remdesivir has been shown to decrease the length of hospital stay in coronavirus disease 2019 (COVID-19) patients requiring supplemental oxygen. However many patients decompensate despite being treated with remdesivir. To identify potential prognostic factors in remdesivir-treated patients, we performed a retrospective cohort study of patients hospitalized at NewYork-Presbyterian Hospital/Weill Cornell Medical Center between March 23, 2020 and May 27, 2020. We identified 55 patients who were treated with remdesivir for COVID-19 and analyzed inflammatory markers and clinical outcomes. C-reactive protein (CRP), d-dimer, and lactate dehydrogenase levels were significantly higher in patients who progressed to intubation or death by 14 days compared to those who remained stable. CRP levels decreased significantly after remdesivir administration in patients who remained nonintubated over the study period. To our knowledge, this is the largest study to date examining inflammatory markers before and after remdesivir administration. Our findings support further investigation into COVID-19 treatment strategies that modify the inflammatory response.


Asunto(s)
Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Antivirales/uso terapéutico , COVID-19/tratamiento farmacológico , COVID-19/mortalidad , SARS-CoV-2/efectos de los fármacos , Adenosina Monofosfato/uso terapéutico , Anciano , Alanina/uso terapéutico , Biomarcadores/sangre , Proteína C-Reactiva/análisis , COVID-19/patología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Inflamación/tratamiento farmacológico , L-Lactato Deshidrogenasa/sangre , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , SARS-CoV-2/inmunología
4.
Redox Rep ; 26(1): 184-189, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34727009

RESUMEN

BACKGROUND: COVID-19 is characterized by the presence of oxidative stress. Vitamin D status has been reviewed as one of the factors that may affect disease severity. The aim of this study was to assess the relationship between serum vitamin D levels, oxidative stress markers and disease severity in hospitalized COVID-19 patients. METHODS: Vitamin D levels were measured in 33 patients with COVID-19. The total antioxidant power and plasma peroxides were determined in serum. RESULTS: Severe COVID-19 patients have lower vitamin D levels (18.39 ± 2.29 ng/mL vs. 28.47 ± 3.05 ng/mL, p < .05) and higher oxidative stress compared to the moderate group. When divided according to serum vitamin D levels, significantly higher values of LDH (604.8 ± 76.98 IU/mL vs. 261.57 ± 47.33 IU/mL) and D-dimer (5978 ± 2028ng/mL vs. 977.7 ± 172 ng/mL) were obtained in the group with vitamin D below 30 ng/mL, followed with significantly higher levels of plasma peroxides (d-ROMs: 414.9 ± 15.82 U.Carr vs. 352.4 ± 18.77 U.Carr; p < .05) and oxidative stress index (OSI: 92.25 ± 6.60 vs. 51.89 ± 6.45; p < .001). CONCLUSION: The presented data provide a justification to consider vitamin D as an important factor that could ameliorate disease severity through its anti-inflammatory and antioxidant effects.


Asunto(s)
COVID-19/sangre , Estrés Oxidativo , Vitamina D/sangre , Adulto , Anciano , Antioxidantes , Biomarcadores/sangre , COVID-19/diagnóstico , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , República de Macedonia del Norte
5.
Ann Med ; 53(1): 1956-1959, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34727801

RESUMEN

PURPOSE: To determine the seroprevalence of SARS-CoV-2 antibodies in eye healthcare workers (EHCW) in the largest ophthalmology centre in Guatemala and factors associated with antibody positivity. METHODS: We conducted a cross sectional sero-survey in all the staff at the largest ophthalmology centre in Guatemala. Serum samples were collected and tested for total antibodies against SARS-CoV-2 employing Roche Elecsys Anti-SARS-CoV-2 Immunoassay. Results were reported as reactive or non-reactive. According to patient exposure the staff were divided into low risk (technicians, domestic and administrative staff) and high risk (nurses, ophthalmologists, anaesthesiologists, and optometrists). Among those with positive antibodies, they were given a survey that included demographic characteristics, COVID-19 exposure, and related symptomatology. Logistic regression was used to determine the factors associated with antibody positivity. RESULTS: On November 25th a total of 94 healthcare workers were sero-surveyed, mean age was 34.15 years (±8.41), most (57.44%) were females. Seroprevalence was 18%, the majority (77%) were in the low-risk group; while 64% at high-risk, tested negative. Those at low exposure, were five times more likely to have antibodies than those at high exposure (OR:5.69; 95% CI 1.69-19.13). Age and gender were not associated to seropositivity. CONCLUSIONS: We found a similar seroprevalence of SARS-CoV-2 antibodies in EHCW to what has been reported in other healthcare groups. Seropositivity was higher among HCW with fewer patient exposure, hence the probability of community transmission.Key messagesEven though eye healthcare workers are believed to be at higher risk of infection, the prevalence of antibodies against SARS-CoV-2 in this group is comparable to what has been reported previously in other healthcare groups.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/epidemiología , Personal de Salud/estadística & datos numéricos , Oftalmólogos/estadística & datos numéricos , SARS-CoV-2/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/diagnóstico , COVID-19/transmisión , COVID-19/virología , Prueba de COVID-19 , Estudios Transversales , Femenino , Guatemala/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Oftalmólogos/psicología , Oftalmología , SARS-CoV-2/genética , Estudios Seroepidemiológicos , Pruebas Serológicas
6.
Front Immunol ; 12: 689866, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34737734

RESUMEN

Rapid recruitment of neutrophils to an inflamed site is one of the hallmarks of an effective host defense mechanism. The main pathway through which this happens is by the innate immune response. Neutrophils, which play an important part in innate immune defense, migrate into lungs through the modulation actions of chemokines to execute a variety of pro-inflammatory functions. Despite the importance of chemokines in host immunity, little has been discussed on their roles in host immunity. A holistic understanding of neutrophil recruitment, pattern recognition pathways, the roles of chemokines and the pathophysiological roles of neutrophils in host immunity may allow for new approaches in the treatment of infectious and inflammatory disease of the lung. Herein, this review aims at highlighting some of the developments in lung neutrophil-immunity by focusing on the functions and roles of CXC/CC chemokines and pattern recognition receptors in neutrophil immunity during pulmonary inflammations. The pathophysiological roles of neutrophils in COVID-19 and thromboembolism have also been summarized. We finally summarized various neutrophil biomarkers that can be utilized as prognostic molecules in pulmonary inflammations and discussed various neutrophil-targeted therapies for neutrophil-driven pulmonary inflammatory diseases.


Asunto(s)
Inmunidad Innata/inmunología , Neutrófilos/inmunología , Neumonía/inmunología , Biomarcadores/sangre , COVID-19/inmunología , Degranulación de la Célula/inmunología , Quimiocinas/inmunología , Ensayos Clínicos como Asunto , Trampas Extracelulares/inmunología , Humanos , Integrinas/inmunología , Pulmón/inmunología , Pulmón/patología , Neutrófilos/efectos de los fármacos , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Receptores de Reconocimiento de Patrones/inmunología , Estallido Respiratorio/inmunología , SARS-CoV-2 , Tromboembolia/inmunología
7.
Sci Rep ; 11(1): 21633, 2021 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-34737330

RESUMEN

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including-among others-four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.


Asunto(s)
COVID-19/metabolismo , Lípidos/sangre , Suero/química , Adulto , Anciano , Biomarcadores/sangre , COVID-19/sangre , Dislipidemias/metabolismo , Femenino , Humanos , Italia , Lipidómica/métodos , Lípidos/análisis , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Pronóstico , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Esfingomielinas/sangre
8.
PLoS One ; 16(11): e0258987, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34793468

RESUMEN

Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients.


Asunto(s)
Biomarcadores/sangre , Células Sanguíneas/patología , COVID-19/mortalidad , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos
9.
Am J Cardiol ; 161: 42-50, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34794617

RESUMEN

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.


Asunto(s)
Aterosclerosis/sangre , Fibrilación Atrial/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Proteómica/métodos , Medición de Riesgo/métodos , Aterosclerosis/complicaciones , Aterosclerosis/epidemiología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Precursores de Proteínas , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología
10.
Sci Rep ; 11(1): 21888, 2021 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-34750495

RESUMEN

Hypercoagulability and the need for prioritizing coagulation markers for prognostic abilities have been highlighted in COVID-19. We aimed to quantify the associations of D-dimer with disease progression in patients with COVID-19. This systematic review and meta-analysis was registered with PROSPERO, CRD42020186661.We included 113 studies in our systematic review, of which 100 records (n = 38,310) with D-dimer data) were considered for meta-analysis. Across 68 unadjusted (n = 26,960) and 39 adjusted studies (n = 15,653) reporting initial D-dimer, a significant association was found in patients with higher D-dimer for the risk of overall disease progression (unadjusted odds ratio (uOR) 3.15; adjusted odds ratio (aOR) 1.64). The time-to-event outcomes were pooled across 19 unadjusted (n = 9743) and 21 adjusted studies (n = 13,287); a strong association was found in patients with higher D-dimers for the risk of overall disease progression (unadjusted hazard ratio (uHR) 1.41; adjusted hazard ratio (aHR) 1.10). The prognostic use of higher D-dimer was found to be promising for predicting overall disease progression (studies 68, area under curve 0.75) in COVID-19. Our study showed that higher D-dimer levels provide prognostic information useful for clinicians to early assess COVID-19 patients at risk for disease progression and mortality outcomes. This study, recommends rapid assessment of D-dimer for predicting adverse outcomes in COVID-19.


Asunto(s)
COVID-19/diagnóstico , COVID-19/inmunología , Productos de Degradación de Fibrina-Fibrinógeno/química , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , COVID-19/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Respiración Artificial , Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Trombofilia/sangre
11.
Rev Med Virol ; 31(6): e2221, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34773448

RESUMEN

The current pandemic caused by SARS-CoV-2 virus infection is known as Covid-19 (coronavirus disease 2019). This disease can be asymptomatic or can affect multiple organ systems. Damage induced by the virus is related to dysfunctional activity of the immune system, but the activity of molecules such as C-reactive protein (CRP) as a factor capable of inducing an inflammatory status that may be involved in the severe evolution of the disease, has not been extensively evaluated. A systematic review was performed using the NCBI-PubMed database to find articles related to Covid-19 immunity, inflammatory response, and CRP published from December 2019 to December 2020. High levels of CRP were found in patients with severe evolution of Covid-19 in which several organ systems were affected and in patients who died. CRP activates complement, induces the production of pro-inflammatory cytokines and induces apoptosis which, together with the inflammatory status during the disease, can lead to a severe outcome. Several drugs can decrease the level or block the effect of CRP and might be useful in the treatment of Covid-19. From this review it is reasonable to conclude that CRP is a factor that can contribute to severe evolution of Covid-19 and that the use of drugs able to lower CRP levels or block its activity should be evaluated in randomized controlled clinical trials.


Asunto(s)
Antiinflamatorios/uso terapéutico , Proteína C-Reactiva/antagonistas & inhibidores , COVID-19/tratamiento farmacológico , Proteínas del Sistema Complemento/inmunología , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , SARS-CoV-2/patogenicidad , Proteína ADAM17/antagonistas & inhibidores , Proteína ADAM17/genética , Proteína ADAM17/inmunología , Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/inmunología , Biomarcadores/sangre , Proteína C-Reactiva/genética , Proteína C-Reactiva/inmunología , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Celecoxib/uso terapéutico , Proteínas del Sistema Complemento/genética , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Citocinas/antagonistas & inhibidores , Citocinas/genética , Citocinas/inmunología , Progresión de la Enfermedad , Doxiciclina/uso terapéutico , Regulación de la Expresión Génica , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
12.
Scand J Immunol ; 94(4): e13095, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34780078

RESUMEN

Inflammation is of critical importance in successful implantation during pregnancy. However, the establishment of maternal immune tolerance towards semi-allograft foetus is more exigent and is achieved predominantly by human leukocyte antigen-G (HLA-G) isoforms with a special emphasis on soluble HLA-G5 (sHLA-G5). Constant inflammation and lack of resolution by anti-inflammatory milieu, due to aberrant expression of critical immunoregulatory molecules such as sHLA-G5 and dysfunctional T helper cells 1 and 2 (Th1-Th2) cytokine shift, can lead to adverse pregnancy outcomes including recurrent pregnancy loss (RPL). Serum samples of 270 pregnant women (135 healthy parous and 135 with a history of RPL) were evaluated for the concentrations of sHLA-G5, interleukin-4 (IL-4) and tumour necrosis factor-alpha (TNF-α) using sandwich enzyme-linked immunosorbent assay (ELISA) and found elevated levels of sHLA-G5 and IL-4 in controls and higher TNF-α levels and TNF-α:IL-4 ratio in patients (P < .05). Stratified data analysis based on the time of sample collection, that is the first and second trimesters exhibited higher sHLA-G5 and IL-4 in both first and second trimesters in controls than patients, while they displayed lower levels concerning TNF-α and TNF-α:IL-4 ratio (P < .05). However, within patients and controls in the first or second trimesters, there was a significant variation concerning sHLA-G5 alone. Further, the outcome of pregnancies studied in the present investigation revealed a significant elevation in sHLA-G5 levels among women with successful pregnancies compared with women who experienced pregnancy loss, therefore, concluding the potential application of sHLA-G5 isoform as a marker in assisting improved pregnancy outcomes.


Asunto(s)
Aborto Habitual/inmunología , Antígenos HLA-G/sangre , Interleucina-4/sangre , Factor de Necrosis Tumoral alfa/sangre , Aborto Habitual/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , India , Análisis Multivariante , Embarazo , Resultado del Embarazo , Isoformas de Proteínas/sangre , Solubilidad , Adulto Joven
14.
Cardiovasc Diabetol ; 20(1): 218, 2021 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-34740359

RESUMEN

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.


Asunto(s)
COVID-19/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Manejo de la Enfermedad , Insuficiencia Cardíaca/epidemiología , Tamizaje Masivo/métodos , Biomarcadores/sangre , COVID-19/sangre , COVID-19/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina A Glucada/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Humanos , Tamizaje Masivo/tendencias , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Pronóstico
15.
JAMA ; 326(19): 1919-1929, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34783839

RESUMEN

Importance: There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). Objective: To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. Design, Setting, and Participants: A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Interventions: Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Main Outcomes and Measures: Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Results: Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Conclusions and Relevance: Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03066804.


Asunto(s)
Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Tolerancia al Ejercicio/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Valsartán/uso terapéutico , Anciano , Aminobutiratos/efectos adversos , Aminobutiratos/farmacología , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacología , Biomarcadores/sangre , Compuestos de Bifenilo/efectos adversos , Compuestos de Bifenilo/farmacología , Método Doble Ciego , Combinación de Medicamentos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Volumen Sistólico , Valsartán/efectos adversos , Valsartán/farmacología , Prueba de Paso
16.
Anticancer Res ; 41(11): 5527-5537, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34732423

RESUMEN

BACKGROUND/AIM: Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS: Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS: Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION: The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.


Asunto(s)
Gastrinas/sangre , Gastritis Atrófica/diagnóstico , Gastroscopía , Infecciones por Helicobacter/diagnóstico , Helicobacter pylori/patogenicidad , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Pruebas Serológicas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antibacterianos/sangre , Biomarcadores/sangre , Biopsia , Ensayo de Inmunoadsorción Enzimática , Femenino , Finlandia , Gastritis Atrófica/sangre , Gastritis Atrófica/microbiología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/microbiología , Helicobacter pylori/inmunología , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Derivación y Consulta , Reproducibilidad de los Resultados , Adulto Joven
17.
Anticancer Res ; 41(11): 5713-5721, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34732444

RESUMEN

BACKGROUND/AIM: Thyroid lobectomy may cause post-lobectomy hypothyroidism. We investigated the difference in levothyroxine (LT4) supplementation and cessation between patients with benign disease and those with papillary thyroid carcinoma (PTC) and found that the rate of LT4 cessation could be decreased after thyroid-stimulating hormone (TSH) suppression in PTC. PATIENTS AND METHODS: We retrospectively reviewed 88 patients with benign tumor and 463 patients with PTC and investigated the risk factors for LT4 supplementation after thyroid lobectomy. RESULTS: During the median follow-up of 73.0 months, 207 (37.6%) patients maintained the euthyroid state, while 344 (62.4%) patients continued LT4 supplementation for LT4 replacement or TSH suppression. In patients with benign tumors, only high pre-TSH level (>1.98 mIU/l) was a significant risk factor (odds ratio [OR]=10.09). However, in patients with PTC, pre-TSH level ≥1.98 mIU/l (OR=3.28), pregnancy planning (OR=2.97), and age ≥42.5 years (OR=1.94) were significant risk factors. Moreover, the most potent risk factor was tumor aggressiveness (OR=4.00), which was found to be more significant than high pre-TSH. The overall rate of LT4 cessation in all patients was 37.6%; however, in the 303 patients who underwent the LT4-Off trial, there was no difference in the rate in the benign tumor, low-risk PTC, and intermediate-risk PTC groups (66.2%, 68.8%, and 70.8%, respectively; p=0.886). CONCLUSION: When post-lobectomy TSH levels were adequate and the risk of recurrence was reduced, LT4 cessation in PTC could be achieved at the same rate as that in benign tumors, regardless of the duration of TSH suppression.


Asunto(s)
Hipotiroidismo/tratamiento farmacológico , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Tiroxina/administración & dosificación , Adulto , Biomarcadores/sangre , Esquema de Medicación , Femenino , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/diagnóstico , Hipotiroidismo/etiología , Masculino , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Tiroidectomía/efectos adversos , Tirotropina/sangre , Tiroxina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
19.
World J Surg Oncol ; 19(1): 302, 2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34657605

RESUMEN

BACKGROUND: Prokineticin 1 (PROK1) was reported as an angiogenic factor, which is associated with tumor progression, cell invasion, and metastasis in colorectal cancer. Although the association between PROK1 expression in primary cancer lesion and patient prognosis was reported, it is unclear whether plasma PROK1 concentration may be a predictive factor in colorectal cancer patients. This study investigated the association between PROK1 concentration in plasma and prognosis in colorectal cancer patients. METHODS: We measured preoperative PROK1 plasma levels using ELISA method, while PROK1 expression in primary cancer lesion was evaluated using immunohistochemistry (IHC). The association between plasma PROK1 levels and cancer-related survival rate (CRS) was evaluated. Additionally, we examined whether simultaneous PROK1 expression in both primary cancer lesions and plasma was correlated with CRS. The cancer-related survival rate was calculated using the Kaplan-Meier method, and survival estimates were compared using the log-rank test. RESULTS: We have gathered eligible 130 CRC patients retrospectively. Out of 130 patients, 61 (46.9%) were positive on IHC in primary cancer, and 69 (53.1%) were negative, while 43 (33.1%) had high-value PROK1 in plasma. Out of these 43, 30 (25.4%) also had concomitant higher IHC expression in primary cancer. The plasma PROK1 levels tended to increase with advancing stages. The plasma PROK1-positive group had a lower 5-year CRS than the negative group (63.6% vs. 88.2%; P = 0.006). Additionally, simultaneous PROK1 expression was associated with a more significant decrease of 5-year CRS than both negative groups in all stages (76.2% vs. 92.5%; P = 0.003) and stage III (59.3% vs. 84.5%; P = 0.047). Multivariate analysis showed simultaneous PROK1 expression was independently associated with worse CRS (HR, 1.97; 95% CI 1.20­3.24, P < 0.01). CONCLUSION: PROK1 expression in preoperative plasma reflects poor prognosis in patients undergoing curative resection for colorectal cancer. The plasma PROK1 level may be a potential predictive marker, especially in stage III colorectal cancer patients.


Asunto(s)
Neoplasias Colorrectales , Hormonas Gastrointestinales , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina , Biomarcadores/sangre , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/cirugía , Hormonas Gastrointestinales/sangre , Humanos , Pronóstico , Estudios Retrospectivos , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/sangre
20.
Isr Med Assoc J ; 23(10): 620-624, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34672442

RESUMEN

BACKGROUND: Cystic periventricular leukomalacia (cPVL) is a strong indicator of subsequent motor and developmental impairments in premature infants. There is a paucity of publications on biomarkers of cPVL. OBJECTIVES: To determine C-reactive protein (CRP) levels during the first week of life of preterm infants who later developed cPVL and to identify the association between CRP levels with perinatal factors. METHODS: We retrospectively included infants ≤ 32 weeks gestation and/or birth weights ≤ 1500 grams; 17 with a cranial ultrasound diagnosis of cPVL and 54 with normal ultrasounds. Serum CRP levels were measured during days 1-7 (CRP1-7d) of life and subdivided into two timing groups: days 1-3 (CRP1-3d) and days 4-7 (CRP4-7d). RESULTS: The cPVL group had significantly higher mean CRP4-7d levels compared to controls (12.75 ± 21.2 vs. 2.23 ± 3.1, respectively, P = 0.03), while CRP1-3d levels were similar. CRP1-7d levels were significantly correlated with maximal fraction of inspired oxygen during the first 12 hours of life (FiO2-12h, r = 0.51, P < 0.001]. Additional risk factors were not associated with CRP levels. CONCLUSIONS: Our finding of elevated CRP4-7d levels and later development of cPVL supports earlier studies on the involvement of inflammation in the pathogenesis of cPVL. Whether CRP could serve as a biomarker of cPVL and its correlation with outcomes, awaits further trials. Furthermore, the correlation between FiO2-12h and CRP1-7d levels suggest that hypoxia and/or hyperoxia may serve as a trigger in the activation of inflammation during the first days of life of preterm infants.


Asunto(s)
Encéfalo/diagnóstico por imagen , Proteína C-Reactiva/análisis , Inflamación/sangre , Leucomalacia Periventricular , Biomarcadores/sangre , Diagnóstico Precoz , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Leucomalacia Periventricular/sangre , Leucomalacia Periventricular/diagnóstico , Masculino , Consumo de Oxígeno/inmunología , Medición de Riesgo , Factores de Riesgo , Ultrasonografía/métodos
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