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Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
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Antineoplásicos Inmunológicos , Carcinoma Hepatocelular , Carcinoma de Pulmón de Células no Pequeñas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias Hepáticas , Neoplasias Pulmonares , Miocarditis , Antineoplásicos Inmunológicos/uso terapéutico , Proteínas Reguladoras de la Apoptosis , Antígeno B7-H1 , Antígeno CTLA-4 , Carcinoma Hepatocelular/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cardiotoxicidad/etiología , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ligandos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Miocarditis/inducido químicamente , Receptor de Muerte Celular Programada 1RESUMEN
The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p < 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.
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Tratamiento Farmacológico de COVID-19 , Sobreinfección , Humanos , Estudios Retrospectivos , SARS-CoV-2 , OxígenoRESUMEN
Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.
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Enfermedad Celíaca , MicroARN Circulante , MicroARNs , Adulto , Biomarcadores , Enfermedad Celíaca/genética , Dieta Sin Gluten , Humanos , MicroARNs/genéticaRESUMEN
Metabolic syndrome (MetS) represents a cluster of disorders that increase the risk of a plethora of conditions, in particular type two diabetes, cardiovascular diseases, and certain types of cancers. MetS is a complex entity characterized by a chronic inflammatory state that implies dysregulations of adipokins and proinflammatory cytokins together with hormonal and growth factors imbalances. Of great interest is the implication of microRNA (miRNA, miR), non-coding RNA, in cancer genesis, progression, and metastasis. The adipose tissue serves as an important source of miRs, which represent a novel class of adipokines, that play a crucial role in carcinogenesis. Altered miRs secretion in the adipose tissue, in the context of MetS, might explain their implication in the oncogenesis. The interplay between miRs expressed in adipose tissue, their dysregulation and cancer pathogenesis are still intriguing, taking into consideration the fact that miRNAs show both carcinogenic and tumor suppressor effects. The aim of our review was to discuss the latest publications concerning the implication of miRs dysregulation in MetS and their significance in tumoral signaling pathways. Furthermore, we emphasized the role of miRNAs as potential target therapies and their implication in cancer progression and metastasis.
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Carcinogénesis/genética , Síndrome Metabólico/genética , MicroARNs/metabolismo , Animales , Humanos , Macrófagos/metabolismo , Macrófagos/patología , MicroARNs/genética , Transducción de Señal/genéticaRESUMEN
Epidemiological studies have strongly associated lower levels of vitamin D and its metabolites with an increased risk of colorectal cancer (CRC). The action of calcitriol, the active metabolite of vitamin D, is mediated by the vitamin D receptor (VDR) that is present in most tissues. In advanced CRC, VDR expression is lowered. Calcitriol has several antineoplastic effects in CRC: it promotes the G1-phase cycle arrest, lowers vascular endothelial growth factor (VEGF) synthesis and acts on tumour stromal fibroblasts to limit cell migration and angiogenesis. Hyperinsulinemia and insulin-like growth factors (IGFs) have been implicated in the pathophysiology of CRC. IGF-1 and IGFBP-3 have been the most studied components of the IGF system. Only 1% of the total serum IGF-1 is free and bioactive, and 80% of it binds to IGFBP-3. IGF-1 and its receptor IGF-1R are known to induce cell proliferation. Both IGF-1 and IGFBP-3 can favour angiogenesis by increasing the transcription of the VEGF gene. A high serum IGF-1/IGFBP-3 ratio is associated with increased risk for CRC. VDR is a transcription factor for the IGFBP-3 gene, and IGF-1 can increase calcitriol synthesis. Studies examining the effect of vitamin D treatment on serum IGF-1 and IGFBP-3 have not been in agreement since different populations, dosages and intervention periods have been used. New vitamin D treatment studies that examine CRC should take in account confounding factors such as obesity or VDR genotypes.
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Calcitriol/metabolismo , Carcinoma/metabolismo , Neoplasias Colorrectales/metabolismo , Receptores de Calcitriol/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Carcinoma/epidemiología , Movimiento Celular , Neoplasias Colorrectales/epidemiología , Factores de Confusión Epidemiológicos , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Hiperinsulinismo/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Neovascularización Patológica/metabolismo , Obesidad/epidemiología , Receptor IGF Tipo 1/metabolismo , Receptores de Calcitriol/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/metabolismoRESUMEN
BACKGROUND: Pruritus and insomnia are common disorders in hemodialysis (HD) patients, with a major clinical impact as they are associated with poor quality of life and increased mortality. Their coexistence and impact on survival in HD patients have rarely been investigated. Our aim is to investigate the survival of HD patients presenting either none, one, or both disorders and to compare certain features between these groups. METHODS: After the inclusion/exclusion criteria, 170 patients treated by HD or online hemodiafiltration were assigned in 4 study groups depending on the presence of either, neither, or both pruritus and insomnia. We analyzed the survival difference between groups after 20 months, and we searched if there were significant differences in terms of clinical and laboratory features. RESULTS: Survival at 20 months was lower in patients with both pruritus and insomnia. Patients with pruritus alone had a lower Kt/V than those with no complaints or insomnia alone. Those with no complaints had lower C-reactive protein and higher albumin levels than patients with insomnia alone or both conditions. CONCLUSION: Pruritus and insomnia should be actively investigated and correlated with some clinical and laboratory features as they have a significant impact on survival in HD patients.
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Fallo Renal Crónico/terapia , Prurito/complicaciones , Diálisis Renal , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Adolescente , Adulto , Proteína C-Reactiva/análisis , Niño , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Estudios Longitudinales , Persona de Mediana Edad , Estudios Prospectivos , Prurito/sangre , Diálisis Renal/efectos adversos , Factores de Riesgo , Trastornos del Inicio y del Mantenimiento del Sueño/sangre , Adulto JovenRESUMEN
Hepatocellular carcinoma (HCC) is a frequently encountered cancer type, and its alarming incidence is explained by genetic and epigenetic alterations. Epigenetic changes may represent diagnostic and prognostic biomarkers of HCC. In this review we discussed deoxyribonucleic acid (DNA) hypomethylation, DNA hypermethylation, and aberrant expression of small non-coding ribonucleic acid (RNA), which could be useful new biomarkers in the early diagnosis of HCC. We selected the articles on human subjects published in English over the past two years involving diagnostic markers detected in body fluids, cancer diagnosis made on histopathological exam, and a control group of those with benign liver disease or without liver disease. These biomarkers need further investigation in clinical trials to develop clinical applications for early diagnosis and management of HCC.
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Carcinoma Hepatocelular/genética , Metilación de ADN , Neoplasias Hepáticas/genética , MicroARNs/genética , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , PronósticoRESUMEN
Hidradenitis suppurativa is a disease with underestimated incidence, consequences and treatment difficulty. Regarded as a minor illness, for the patient it is disabling physically and socially, and for the doctor it is a challenge in choosing the appropriate treatment. We present the case of a 28-year-old man who presented with an advanced and persistent form of hidradenitis treated in a general surgery department. Solving the case combined conservative and surgical treatment (wide excisions, plasties with fasciocutaneous superior gluteal artery perforator flap, thoracodorsal artery perforator flap, free anterolateral thigh flap). This case illustrates the problems raised by a seemingly trivial disease. KEY WORDS: Fasciocutaneous Superior Gluteal Artery Perforator Flap, Follicular Occlusion, Free Anterolateral Thigh Flap, Hidradenitis Suppurativa, Skin Ulcer, Skin Fold, Thoracodorsal Artery Perforator Flap.
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Colgajos Tisulares Libres , Hidradenitis Supurativa , Úlcera Cutánea , Masculino , Humanos , Adulto , Hidradenitis Supurativa/cirugía , Extremidad Inferior , Aorta AbdominalRESUMEN
BACKGROUND AND OBJECTIVES: the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. MATERIALS AND METHODS: systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. RESULTS: a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.
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BACKGROUND: During the last years, the COVID-19 pandemic meets the pandemic generated by obesity, raising many questions regarding the outcomes of those with severe forms of infection. METHODS: The present systematic review summarises and analyses the data providing evidence for or against the "obesity-paradox" in COVID-19 patients. After applying the inclusion and exclusion criteria, 23 studies were included. We also analysed the presumably underlying basic mechanisms. RESULTS: The patients with a body mass index (BMI) of 30-40 kg/m2 presented severe symptoms that led to intensive care unit (ICU) admission but not increased death rate. Those with a higher degree of obesity, with a BMI higher than 40 kg/m2, led to a rise in the death rate, particularly in young patients. Obesity was associated with a higher rate of ICU admission but was not determined as an independent predictor of increased mortality. In contrast, some studies suggest a strong association between obesity or morbid obesity and the risk of death. CONCLUSIONS: The existence of "obesity-paradox" cannot be stated; our study presents obesity as a critical risk factor in the evolution of COVID-19.
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Glucose transporter type 1 (Glut1) is the main transporter involved in the cellular uptake of glucose into many tissues, and is highly expressed in the brain and in erythrocytes. Glut1 deficiency syndrome is caused mainly by mutations of the SLC2A1 gene, impairing passive glucose transport across the blood-brain barrier. All age groups, from infants to adults, may be affected, with age-specific symptoms. In its classic form, the syndrome presents as an early-onset drug-resistant metabolic epileptic encephalopathy with a complex movement disorder and developmental delay. In later-onset forms, complex motor disorder predominates, with dystonia, ataxia, chorea or spasticity, often triggered by fasting. Diagnosis is confirmed by hypoglycorrhachia (below 45 mg/dL) with normal blood glucose, 18F-fluorodeoxyglucose positron emission tomography, and genetic analysis showing pathogenic SLC2A1 variants. There are also ongoing positive studies on erythrocytes' Glut1 surface expression using flow cytometry. The standard treatment still consists of ketogenic therapies supplying ketones as alternative brain fuel. Anaplerotic substances may provide alternative energy sources. Understanding the complex interactions of Glut1 with other tissues, its signaling function for brain angiogenesis and gliosis, and the complex regulation of glucose transportation, including compensatory mechanisms in different tissues, will hopefully advance therapy. Ongoing research for future interventions is focusing on small molecules to restore Glut1, metabolic stimulation, and SLC2A1 transfer strategies. Newborn screening, early identification and treatment could minimize the neurodevelopmental disease consequences. Furthermore, understanding Glut1 relative deficiency or inhibition in inflammation, neurodegenerative disorders, and viral infections including COVID-19 and other settings could provide clues for future therapeutic approaches.
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Currently, adipose tissue is considered an endocrine organ, however, there are still many questions regarding the roles of adipokines-leptin and ghrelin being two adipokines. The purpose of the study was to assess the relationship between the adipokines and their ratio with obesity and diabetes. Methods: Sixty patients (mean age 61.88 ± 10.08) were evaluated. Cardiovascular risk factors, leptin, ghrelin, and insulin resistance score values were assessed. The patients were classified according to their body mass index (BMI) as normal weight, overweight, and obese. Results: 20% normal weight, 51.7% overweight, 28.3% obese, and 23.3% diabetic. Obese patients had higher leptin values (in obese 34,360 pg/mL vs. overweight 18,000 pg/mL vs. normal weight 14,350 pg/mL, p = 0.0049) and leptin/ghrelin ratio (1055 ± 641 vs. 771.36 ± 921 vs. 370.7 ± 257, p = 0.0228). Stratifying the analyses according to the presence of obesity and patients' gender, differences were found for leptin (p = 0.0020 in women, p = 0.0055 in men) and leptin/ghrelin ratio (p = 0.048 in women, p = 0.004 in men). Mean leptin/BMI and leptin/ghrelin/BMI ratios were significantly higher, and the ghrelin/BMI ratio was significantly lower in obese and diabetic patients. In conclusion, obesity and diabetes are associated with changes not only in the total amount but also in the level of adipokines/kg/m2. Changes appear even in overweight subjects, offering a basis for early intervention in diabetic and obese patients.
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Hepatitis Viral Humana/complicaciones , Ácido Hialurónico/sangre , Fallo Renal Crónico/terapia , Cirrosis Hepática/complicaciones , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Diálisis Renal , RumaníaRESUMEN
BACKGROUND: Diabetes and obesity are increasingly significant public health issues. The aim of this study was to evaluate the relationship between adipocytokines (leptin, ghrelin, and chemerin), inflammation (sVCAM1-soluble vascular adhesion molecule 1, sICAM1-soluble intercellular adhesion molecule 1), and insulin resistance in the presence of obesity and diabetes mellitus. METHODS: 88 subjects, with a mean age of 61.96 ± 10.15 years, 75% of whom were women, were evaluated (in order to consider different associations between obesity and diabetes, subjects were categorized into four groups). RESULTS: Overall, we found significant correlations between sICAM1-sVCAM1 rho = 0.426 and ghrelin-chemerin rho = -0.224. In the obesity + diabetes group, leptin correlated with sICAM1 rho = 0.786, and sVCAM1 negatively with glycemia/insulin rho = -0.85. Significant differences were found between the groups regarding sVCAM1 (p = 0.0134), leptin (p = 0.0265) and all insulin resistance scores, with differences influenced by the subjects' gender. In conclusion, although there are currently many unknown aspects of the release and the role of various adipokines, in particular chemerin, its implication in early glucose metabolism dysregulation disorders seems very likely.
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We present the clinical observation of a female patient with cystic peritoneal malignant mesothelioma developed in the thickness of the abdominal wall. The diagnosis included several steps: tumor classification as mesothelioma, tumor differentiation from reactive mesothelial hyperplasia, establishment of the malignant nature and differentiation from other malignant peritoneal tumors. Relapse in about one year after surgery and about six months after the end of chemotherapy also claim malignancy of the tumor. The particular tumor location in the thickness of the abdominal muscles, seemingly without involvement of the parietal peritoneum, in a patient with a history of caesarean operation, questions its development out of ectopic tissue embedded in scar from previous surgery. KEY WORDS: Abdominal wall, Caesarian operation Cystic malignant peritoneal mesothelioma, CK5/6, p53.
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Endothelial nitric oxide synthase (NOS3 or eNOS) is the enzyme responsible for the highest production of nitric oxide, with the greatest impact on the cardiovascular system, encoded by the eNOS gene, which presents various polymorphisms. ENOS gene polymorphisms play an important role in the response to drugs affecting nitric oxide (NO) signaling. This review discusses the pharmacogenetic impact of eNOS polymorphisms on the response to drugs affecting NO activity: angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, calcium blockers, beta-blockers, diuretics, phosphodiesterase inhibitors, and statins. The identification of biomarkers that accurately predict particular phenotypes is a challenge that needs additional large studies, in different populations. Efforts should be oriented towards a more accurate evaluation of the effects of eNOS genetic variants on biochemical parameters reflecting eNOS gene expression and enzymatic activity, in different diseases, as well as following drug treatment. This approach will allow for a better understanding of the role of eNOS genetic variants in cardiovascular disease progression and for cardiovascular drug therapy optimization.
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Alelos , Sustitución de Aminoácidos , Fármacos Cardiovasculares/farmacología , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Animales , Biomarcadores , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Óxido Nítrico/metabolismo , Farmacogenética , Transducción de Señal/efectos de los fármacosRESUMEN
INTRODUCTION: Insomnia, muscular cramps, pruritus and postdialysis recovery time (RT) are quality-of-life parameters that affect hemodialysis (HD) patients physically and mentally. METHODS: We included 171 end-stage renal disease patients: 115 on high-flux HD and 56 on online hemodiafiltration (HDF). Patients were asked "How long does it take you to recover from a dialysis session?" and they evaluated intensity (absent, mild, medium and severe) of insomnia, muscular cramps and pruritus in the past 4 weeks. We sought associations of RT, insomnia, muscular cramps and pruritus with themselves and age, dialysis vintage, sex, body mass index, hemoglobin, albumin, C-reactive protein (CRP), Daugirdas single-pool Kt/V (Kt/V), ultrafiltration volume, blood processed volume and vascular access type. RESULTS: Insomnia absence correlated with muscular cramps absence (p = 0.01), arteriovenous fistula (AVF) presence (p = 0.02) and lower CRP (p = 0.003). Muscular cramps absence associated pruritus absence (p = 0.007) and AVF (p = 0.001). Absent pruritus patients were younger (p = 0.04), had higher Kt/V (p = 0.01) and more AVF (p = 0.02). Men insomnia was more severe in HD than HDF and albumin related (p = 0.007), while CRP was lower in absent pruritus. Women insomnia associated with muscular cramps (p = 0.04) and vascular access (p = 0.03), as was pruritus (p = 0.03). RT had no relations with any parameter. CONCLUSIONS: HD patients with AVF have less insomnia, muscular cramps and pruritus. Insomnia is associated with muscular cramps and inflammation. Pruritus is worse in older patients, is diminished with increased dialysis efficiency and is associated with higher CRP in men. There is no difference between HD and HDF patients, except more severe insomnia for HD in men.
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Derivación Arteriovenosa Quirúrgica , Hemodiafiltración/efectos adversos , Fallo Renal Crónico/terapia , Calambre Muscular/etiología , Prurito/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de TiempoRESUMEN
Chronic liver diseases represent a significant public health problem worldwide. The degree of liver fibrosis secondary to these diseases is important, because it is the main predictor of their evolution and prognosis. Hyaluronic acid is studied as a non-invasive marker of liver fibrosis in chronic liver diseases, in an attempt to avoid the complications of liver puncture biopsy, considered the gold standard in the evaluation of fibrosis. We review the advantages and limitations of hyaluronc acid, a biomarker, used to manage patients with chronic viral hepatitis B or C infection, non-alcoholic fatty liver disease, HIV-HCV coinfection, alcoholic liver disease, primary biliary cirrhosis, biliary atresia, hereditary hemochromatosis and cystic fibrosis.
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PURPOSE: Serum hyaluronic acid (sHA) is studied as a noninvasive marker of liver fibrosis (F) in chronic B and C viral hepatitis in general population but less in end-stage renal disease patients undergoing hemodialysis. METHODS: We evaluated sHA as a noninvasive biomarker of F in a multicenter prospective, transversal, and observational study which included 52 end-stage renal disease patients with chronic B (14) and C (38) viral hepatitis (age 55.57 ± 14.46 years, dialysis vintage 132.59 ± 86.02 months). RESULTS: Of the noninvasive tests analyzed, only sHA, APRI, and FIB4 index were able to differentiate patients with F1 (sHA p = 0.006; APRI p = 0.031; FIB4 p = 0.016). No statistically significant differences were found between sHA and APRI, ASAT/ALAT ratio, and FIB4 index in detecting F1 a (p > 0.02). sHA seemed to be more efficient than APRI, ASAT/ALAT ratio, and FIB4 index, having the highest estimated AUC value. The sHA threshold value for F1 was equal to 33.46 ng/mL, with the following estimated values of the performance indicators: Se 88.46 % and Sp 50 %. sHA was the only noninvasive test of the studied tests that could determine F2 (p = 0.002), with a threshold value of 80.24 ng/mL (Se 63 %, Sp 88 %), and F3 (p = 0.008), with a threshold value of 88.54 ng/mL (Se 60 %, Sp 84 %). None of the studied noninvasive tests could determine F4. CONCLUSIONS: In patients with chronic B and C viral hepatitis undergoing hemodialysis, sHA may be a useful biomarker for the liver fibrosis grades: F1-mild, F2-moderate, and F3-severe, but it does not differentiate between chronic hepatitis (F1-F3) and liver cirrhosis (F4).
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Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Hepatitis B Crónica , Hepatitis C Crónica , Ácido Hialurónico/sangre , Fallo Renal Crónico , Cirrosis Hepática , Adulto , Anciano , Biomarcadores/sangre , Diagnóstico Diferencial , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Diálisis Renal , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF. METHODS: Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly-weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months--albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF. RESULTS: In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months. CONCLUSIONS: Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.