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1.
N Engl J Med ; 384(6): 512-520, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-33567191

RESUMEN

BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma. METHODS: In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]). RESULTS: A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved. CONCLUSIONS: In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Administración Tópica , Anciano , Método Doble Ciego , Inhibidores Enzimáticos/efectos adversos , Cara/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pomadas/uso terapéutico , Polimerizacion/efectos de los fármacos , Cuero Cabelludo/patología , Piel/patología , Tubulina (Proteína)/metabolismo
2.
Trials ; 22(1): 59, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33451350

RESUMEN

BACKGROUND: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of overall clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in this data by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications to quantify the number of trials missing results for drugs potentially being repurposed for COVID-19. METHODS: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance. RESULTS: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. Tabular results were available on ClinicalTrials.gov for 1172 (31.2%) completed trials. A further 1066 (28.4%) had published results in the academic literature, but did not report results on ClinicalTrials.gov . Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%). CONCLUSIONS: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause unnecessary additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.


Asunto(s)
Antivirales/uso terapéutico , Ensayos Clínicos como Asunto , Inhibidores Enzimáticos/uso terapéutico , Sistema de Registros , Informe de Investigación , Amidas/uso terapéutico , Combinación de Medicamentos , Reposicionamiento de Medicamentos , Medicina Basada en la Evidencia , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , PubMed , Pirazinas/uso terapéutico , Proyectos de Investigación , Ritonavir/uso terapéutico
3.
Trials ; 22(1): 44, 2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33430933

RESUMEN

OBJECTIVES: The primary objective of this study is to evaluate the therapeutic potential of hydroxychloroquine (HCQ) in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo. The study hypothesis is that treatment with HCQ will reduce the risk of hospitalization because of Covid-19 infection, and the sample size estimate of the study is based on the need to test this hypothesis. The secondary objectives of the study are: to evaluate the safety and tolerability of HCQ in the treatment of adult patients with PCR-confirmed Covid-19 infection in a primary open-care setting, as compared to placebo; to collect experience of the use of HCQ in the treatment of Covid-19 infection in outpatients, in order to be able to identify patient characteristics that predict specific treatment responses (favourable or unfavourable); this objective will also be addressed by post-hoc subgroup analysis of the study results and by meta-analysis of pooled patient data from other clinical trials of HCQ in outpatients; and to evaluate the impact of Covid-19 infection and its treatment on the mental health and well-being of the study participants. In addition, if the data allow, the study has the following exploratory objectives: to evaluate the extent and duration of SARS-CoV-2 viral shedding by PCR testing of nasopharyngeal swab samples in study subjects treated with HCQ, as compared to placebo; to evaluate the extent and time course of SARS-CoV-2 virus-specific antibody responses in serum of study subjects treated with HCQ, as compared to placebo; to evaluate other possible biomarker changes in blood in study subjects treated with HCQ, as compared to placebo; to explore the possible effects of genetic variation in drug metabolizing enzymes on HCQ-related outcomes in the study population; to explore the associations of HCQ-related outcome variables with other patient characteristics, e.g. HLA haplotypes, HCQ concentrations, demographic variables, disease history and concomitant medications. TRIAL DESIGN: This is a phase 2, placebo-controlled, double-blind, randomized, parallel-group treatment trial comparing HCQ with placebo in outpatients with Covid-19 infection. Participants will be randomized in a 1:1 ratio to the two treatment arms. PARTICIPANTS: Main inclusion criteria: 1. Males and females >40 years of age, or 18-40 years of age with one or both of the following: i. diabetes mellitus (type 1 or type 2); ii. BMI > 35 kg/m2; 2. Valid independent informed consent obtained; 3. Symptoms typical of Covid-19 infection, according to criteria specified in the study protocol. The onset of symptoms must be within 5 days of enrolment; 4. Positive SARS-CoV-2 PCR test result of a nasopharyngeal swab sample. Main exclusion criteria: 1. Suspected severe or moderately severe pneumonia, presenting with any of the following: respiratory rate > 26 breaths/min; significant respiratory distress; or SpO2 ≤94% on room air; 2. Requiring treatment in the hospital, according to the treating physician's judgement; 3. Any contraindication to treatment with HCQ; 4. Pregnancy or lactation. The trial will be conducted at seven study sites in a primary public health care setting in the region of Satakunta, Finland. INTERVENTION AND COMPARATOR: Participants will be randomized to receive either HCQ capsules at 300 mg twice a day for one day and then 200 mg twice a day for 6 days, or placebo capsules for 7 days. MAIN OUTCOMES: The primary endpoint of the study is the number of hospitalizations due to Covid-19 infection within four weeks of entry into the study. The secondary endpoints of the study include the following: duration and severity of Covid-19-related symptoms, as reported by daily self-assessments; number of Intensive Care Unit treatment episodes due to Covid-19 infection within four weeks of entry into the study; number of deaths due to Covid-19 infection within four weeks of entry into the study; number of treatment-related adverse events (AEs) and serious AEs (SAEs); all-cause hospitalizations and mortality within six months of entry into the study; and self-assessed symptoms of anxiety, as assessed with repeated administration of the Generalized Anxiety Disorder 7-item scale (GAD-7). The exploratory endpoints of the study include the following: extent and duration of SARS-CoV-2 viral shedding and virus-specific antibody responses in serum; and possible other blood biomarker changes. RANDOMISATION: Eligible study participants are randomly allocated into two treatment arms (1:1 ratio). The randomization list has been generated using Viedoc™ (Viedoc Technologies AB, Uppsala, Sweden) that is used as an electronic data capture system for this study. BLINDING (MASKING): The participants and all study personnel remain blinded to the treatment allocation by having both IMPs packed in identical containers. Masking of the treatments was performed by re-formulation of the IMPs so that the HCQ capsules and the placebo capsules have identical appearance. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 600 participants are to be randomised with 300 in each arm. TRIAL STATUS: Protocol version 2, dated 14 July 2020; recruitment is expected to start in December, 2020, and to be completed in June, 2021. TRIAL REGISTRATION: EudraCT 2020-002038-33 , registered 26 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). The protocol has been redacted to conform with privacy regulations by deleting the names and contact information of individuals mentioned in the protocol but not listed as authors in this communication. In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Atención Ambulatoria , Inhibidores Enzimáticos/uso terapéutico , Hospitalización/estadística & datos numéricos , Hidroxicloroquina/uso terapéutico , Atención Primaria de Salud , Adolescente , Adulto , Anciano , Ansiedad/psicología , /mortalidad , Causas de Muerte , Comorbilidad , Diabetes Mellitus/epidemiología , Método Doble Ciego , Humanos , Persona de Mediana Edad , Mortalidad , Obesidad/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Esparcimiento de Virus , Adulto Joven
4.
Medicine (Baltimore) ; 100(1): e24093, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33429774

RESUMEN

RATIONALE: Henoch-Schönlein Purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. In majority of the cases, the disease is self-limited. Relapses can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. The efficacy and safety of steroidal treatment in treating HSP is still controversial. Immunosuppressive treatment of HSP nephritis is used in patients with severe renal involvement (nephrotic range proteinuria and/or progressive renal impairment). The literature on immunosuppressive treatment of severe HSP without kidney involvement is scanty. PATIENTS CONCERNS: We report 2 case reports of 2 adolescents affected from Henoch-Schönlein Purpura and severe gastrointestinal involvement. Both patients presented a poor response to steroids treatment. DIAGNOSES: The diagnosis of HSP was made according to the diagnostic criteria published by European League against Rheumatism and Pediatric Rheumatology European Society in 2006. INTERVENTIONS: In consideration of the recurrence of the Henoch Schönlein Purpura and the gastrointestinal involvement, we decided to start Mycophenolate Mofetil treatment. OUTCOMES: In both patients all clinical manifestations resolved in few days. LESSONS: In our cases of HSP with gastrointestinal involvement Mycophenolate Mofetil treatment has been very effective. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistent, recurrent, or complicated Henoch Schönlein Purpura in children.


Asunto(s)
Tracto Gastrointestinal/efectos de los fármacos , Ácido Micofenólico/uso terapéutico , Púrpura de Schoenlein-Henoch/tratamiento farmacológico , Adolescente , Niño , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Tracto Gastrointestinal/fisiopatología , Humanos , Masculino , Ácido Micofenólico/farmacología , Púrpura de Schoenlein-Henoch/fisiopatología , Recurrencia
5.
Nat Commun ; 12(1): 421, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462210

RESUMEN

Multiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on bone marrow mesenchymal stromal cells (MSCs). MM-MSCs exhibit abnormal transcriptomes, suggesting the involvement of epigenetic mechanisms governing their tumor-promoting functions and prolonged osteoblast suppression. Here, we identify widespread DNA methylation alterations of bone marrow-isolated MSCs from distinct MM stages, particularly in Homeobox genes involved in osteogenic differentiation that associate with their aberrant expression. Moreover, these DNA methylation changes are recapitulated in vitro by exposing MSCs from healthy individuals to MM cells. Pharmacological targeting of DNMTs and G9a with dual inhibitor CM-272 reverts the expression of hypermethylated osteogenic regulators and promotes osteoblast differentiation of myeloma MSCs. Most importantly, CM-272 treatment prevents tumor-associated bone loss and reduces tumor burden in a murine myeloma model. Our results demonstrate that epigenetic aberrancies mediate the impairment of bone formation in MM, and its targeting by CM-272 is able to reverse MBD.


Asunto(s)
Antineoplásicos/farmacología , Enfermedades Óseas/tratamiento farmacológico , Metilación de ADN/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/uso terapéutico , Enfermedades Óseas/diagnóstico , Enfermedades Óseas/genética , Enfermedades Óseas/patología , Médula Ósea/patología , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Epigénesis Genética/efectos de los fármacos , Femenino , Fémur/diagnóstico por imagen , Fémur/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antígenos de Histocompatibilidad/metabolismo , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Masculino , Células Madre Mesenquimatosas/patología , Ratones , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Ensayos Antitumor por Modelo de Xenoinjerto
6.
J Ethnopharmacol ; 264: 113296, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-32841690

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Flourensia fiebrigii is a plant used in traditional medicine in the Argentine Calchaquí Valley as purgative, expectorant, anti-rheumatic and anti-inflammatory. AIM OF THE STUDY: The aim of this study was to analyze the macroscopic and microscopic characteristics of F. fiebrigii leaf and stem, the phytochemical composition of leaves ethanolic extracts and to validate its traditional use as anti-rheumatic and anti-inflammatory. MATERIALS AND METHODS: The macroscopic and microscopic description of F. fiebrigii leaf and stem was carried out. Two extracts (immersions and tinctures) from leaves were obtained. The phytochemical analysis and UHPLC-OT-MS metabolome fingerprinting of both extracts were performed. The anti-rheumatic and anti-inflammatory activities of both extracts were determined using enzymatic inhibition assays of xanthine-oxidase (XOD), secretory phospholipase A2 (sPLA2) and lipoxygenase (LOX). RESULTS: The macroscopic and micrographic characters of F. fiebrigii were described to allow the botanical characterization of the plant species. The leaves extracts showed a high level of phenolic compounds with similar chromatographic patterns. Forty-five compounds were identified based on UHPLC-OT-MS including several sesquiterpenes, chalcones, flavonoids, isoflavonoids, a lignan and phenylpropanoids phenolic acids that have been identified for the first time in this plant species. F. fiebrigii extracts were able to inhibit the XOD activity and, consequently, the formation of uric acid and reactive oxygen species, primary cause of diseases, such as gouty arthritis (IC50 values of 1.10-2.12 µg/mL). Pro-inflammatory enzymes like sPLA2 and LOX were also inhibited by F. fiebrigii extracts (IC50 values of 22.00-2.20 µg/mL) decreasing the production of inflammation mediators. CONCLUSIONS: The present work validates the traditional medicinal use of F. fiebrigii as anti-rheumatic and anti-inflammatory through the use of enzymatic assays. The presence of several chemical compounds with demonstrated anti-rheumatic and anti-inflammatory properties also supports the bioactivity of the F. fiebrigii.


Asunto(s)
Antiinflamatorios/uso terapéutico , Asteraceae , Inhibidores Enzimáticos/uso terapéutico , Componentes Aéreos de las Plantas , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Argentina/etnología , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/enzimología , Inflamación/etnología , Componentes Aéreos de las Plantas/citología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología
7.
Toxicol Lett ; 339: 12-19, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33359020

RESUMEN

Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17ß-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Based on their minimal inhibitory effects on the respiratory rate of mitochondria and CS and complex I activity, six novel compounds were selected for further testing. Assuming that inhibition of MAO-B could be a desirable effect of AD drugs, only AG18051 and one new compound met the criteria for MAO-B inhibition with minimal drug-induced effects on mitochondrial respiration. In conclusion, our in vitro screening of mitochondrial effect of novel potential AD drugs has enabled the selection of the most promising molecules for further testing that are relatively safe in terms of drug-induced mitochondrial toxicity.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , 17-Hidroxiesteroide Deshidrogenasas/toxicidad , Respiración de la Célula/efectos de los fármacos , Inhibidores Enzimáticos/toxicidad , Inhibidores Enzimáticos/uso terapéutico , Mitocondrias/efectos de los fármacos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Animales , Humanos , Modelos Animales , Porcinos
8.
Eur J Med Chem ; 211: 113071, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33341650

RESUMEN

Indoleamine-2,3-dioxygenase 1 (IDO1) catalyses the first and rate limiting step of kynurenine pathway accounting for the major contributor of L-Tryptophan degradation. The Kynurenine metabolites are identified as essential cofactors, antagonists, neurotoxins, immunomodulators, antioxidants as well as carcinogens. The catalytic active site of IDO1 enzyme consists of hydrophobic Pocket-A positioned in the distal heme site and remains connected to a second hydrophobic Pocket-B towards the entrance of the active site. IDO1 enzyme also relates directly to the modulation of the innate and adaptive immune system. Various studies proved that the over expression of IDO1 enzyme play a predominant role in the escape of immunity during cancer progression. Recently, there has been considerable interest in evaluating the potential of IDO1 inhibitors to mobilize the body's immune system against solid tumours. In the last two decades, enormous attempts to advance new IDO1 inhibitors are on-going both in pharmaceutical industries and in academia which resulted in the discovery of a diverse range of selective and potent IDO1 inhibitors. The IDO1 inhibitors have therapeutic utility in various diseases and in the near future, it may have utility in the treatment of COVID-19. Despite various reviews on IDO1 inhibitors in last five years, none of the reviews provide a complete overview of diverse chemical space including naturally occurring and synthetic IDO1 inhibitors with detailed structure activity relationship studies. The present work provides a complete overview on the IDO1 inhibitors known in the literature so far along with the Structure-Activity Relationship (SAR) in each class of compounds.


Asunto(s)
/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Productos Biológicos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Humanos , Relación Estructura-Actividad
9.
Cell Prolif ; 54(2): e12963, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33314500

RESUMEN

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In this review, we summarize the current understanding of CSCs and their role in cancer progression, and provide an overview of epigenetic alterations seen in CSCs. Importantly, we focus on primary cancer therapies that target the epigenetic modification of CSCs by the use of specific chemical inhibitors, such as histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) inhibitors and microRNA-based (miRNA-based) therapeutics.


Asunto(s)
Epigénesis Genética , Células Madre Neoplásicas/metabolismo , Antagomirs/metabolismo , Antagomirs/farmacología , Antagomirs/uso terapéutico , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Transición Epitelial-Mesenquimal , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/efectos de los fármacos
10.
Cell Prolif ; 54(2): e12974, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33382511

RESUMEN

Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and survival. STAT proteins are conserved among eukaryotes and are important for biological functions of embryogenesis, immunity, haematopoiesis and cell migration. STAT3 is widely expressed and located in the cytoplasm in an inactive form. STAT3 is rapidly and transiently activated by tyrosine phosphorylation by a range of signalling pathways, including cytokines from the IL-6 family and growth factors, such as EGF and PDGF. STAT3 activation and subsequent dimer formation initiates nuclear translocation of STAT3 for the regulation of target gene transcription. Four STAT3 isoforms have been identified, which have distinct biological functions. STAT3 is considered a proto-oncogene and constitutive activation of STAT3 is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas. In this review, we focus on recent progress on STAT3 and osteosarcoma (OS). Notably, STAT3 is overexpressed and associated with the poor prognosis of OS. Constitutive activation of STAT3 in OS appears to upregulate the expression of target oncogenes, leading to OS cell transformation, proliferation, tumour formation, invasion, metastasis, immune evasion and drug resistance. Taken together, STAT3 is a target for cancer therapy, and STAT3 inhibitors represent potential therapeutic candidates for the treatment of OS.


Asunto(s)
Neoplasias Óseas/patología , Osteosarcoma/patología , Factor de Transcripción STAT3/metabolismo , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Resistencia a Antineoplásicos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/uso terapéutico , Humanos , Metástasis de la Neoplasia , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Pronóstico , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/genética
11.
Eur Rev Med Pharmacol Sci ; 24(23): 12527-12535, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336773

RESUMEN

Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.


Asunto(s)
/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Miocarditis/inmunología , /metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis , Factor Natriurético Atrial/uso terapéutico , Azetidinas/uso terapéutico , Compuestos de Bencilo/uso terapéutico , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Glicoproteínas/uso terapéutico , Humanos , Hipoxia/metabolismo , Hipoxia/terapia , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Isquemia Miocárdica/metabolismo , Miocarditis/metabolismo , Miocarditis/terapia , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Terapia por Inhalación de Oxígeno , Respiración Artificial , Moduladores de los Receptores de fosfatos y esfingosina 1/uso terapéutico , Inhibidores de Tripsina/uso terapéutico , Inhibidores del factor de Necrosis Tumorales/uso terapéutico , alfa-Metiltirosina/uso terapéutico
12.
Eur Rev Med Pharmacol Sci ; 24(23): 12593-12608, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336780

RESUMEN

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antivirales/uso terapéutico , /tratamiento farmacológico , /terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Amidas/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Neutralizantes/uso terapéutico , Antiparasitarios/uso terapéutico , Cannabinoides/uso terapéutico , Cloroquina/uso terapéutico , Inactivadores del Complemento/uso terapéutico , Dexametasona/uso terapéutico , Combinación de Medicamentos , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunización Pasiva , Indoles/uso terapéutico , Interferones/uso terapéutico , Ivermectina/uso terapéutico , Lopinavir/uso terapéutico , Pirazinas/uso terapéutico , Ritonavir/uso terapéutico , Teicoplanina/uso terapéutico , Tetraciclinas/uso terapéutico , Tiazoles/uso terapéutico
13.
J Med Case Rep ; 14(1): 246, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33339534

RESUMEN

BACKGROUND: In December 2019, a new coronavirus (named severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) spread from China, causing a pandemic in a very short time. The main clinical presentation of SARS-CoV-2 infection (COVID-19, coronavirus disease-2019) is pneumonia, but several cardiovascular complications may also occur (e.g., acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure and cardiogenic shock). Direct or indirect mechanisms induced by SARS-CoV-2 could be implicated in the pathogenesis of these events. CASE PRESENTATION: We report herein the third case of COVID-19 autoimmune haemolytic anaemia (AIHA) reported so far, which occurredwithout any other possible explanations in a Caucasian patient. The patient also suffered from ST-elevation myocardial injury. CONCLUSIONS: Both complications occurred quite late after COVID-19 diagnosis and were probably precipitated by systemic inflammation, as indicated by a significant delayed increase in inflammatory markers, including interleukin-6 (IL-6).


Asunto(s)
Anemia Hemolítica Autoinmune/sangre , Infecciones Asintomáticas , Proteína C-Reactiva/inmunología , Interleucina-6/inmunología , Infarto del Miocardio con Elevación del ST/diagnóstico , Anciano de 80 o más Años , Anemia Hemolítica Autoinmune/tratamiento farmacológico , Anemia Hemolítica Autoinmune/etiología , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , /tratamiento farmacológico , Prueba de Coombs , Electrocardiografía , Inhibidores Enzimáticos/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prednisolona/uso terapéutico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/etiología
14.
Eur Rev Med Pharmacol Sci ; 24(24): 13089-13097, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33378062

RESUMEN

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Hidroxicloroquina/uso terapéutico , Retractación de Publicación como Asunto , Grupo de Ascendencia Continental Africana/estadística & datos numéricos , Factores de Edad , Grupo de Ascendencia Continental Asiática/estadística & datos numéricos , /epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Bases de Datos Factuales , Diabetes Mellitus/epidemiología , Quimioterapia Combinada , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/epidemiología , Huésped Inmunocomprometido/inmunología , Difusión de la Información , Macrólidos/uso terapéutico , Obesidad/epidemiología , Puntuaciones en la Disfunción de Órganos , Factores Protectores , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Fumar/epidemiología
15.
Indian J Tuberc ; 67(4S): S147-S154, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33308661

RESUMEN

COVID 19 infection is unarguably the worst pandemic of this century. Till date there is no promising drug and vaccine available to treat this deadly viral infection. In the early phase chloroquine phosphate and hydroxychloroquine sulphate have been used to fight this illness on the basis of handful observational and small randomized and small-randomized studies. The paucity of clinical evidences of an unequivocal beneficial effect of chloroquine and hydroxychloroquine on COVID-19 has resulted in the passionate use of the drug for moderate to severe cases only and stimulated the need for large clinical trials for this and other molecules. In this review, we describe in brief the mechanism of action, the clinical studies, factors for cardiac toxicity, guidelines and future directions for hydroxychloroquine use in management of COVID-19 infection.


Asunto(s)
/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Hidroxicloroquina/farmacología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico
16.
Respiration ; 99(12): 1145-1153, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33316806

RESUMEN

Treatment with immunomodulators, such as intravenous immunoglobulin (IVIG), may attenuate inflammatory responses observed in the severe stages of acute respiratory distress syndrome (ARDS) caused by coronavirus disease 19 (COVID-19). We retrospectively evaluated the clinical courses of 12 COVID-19 patients who received IVIG at various stages of their illness, including within the first 72 h of clinical presentation, after initiation of mechanical ventilation, and after prolonged ventilation and ICU stay. The patients included 9 men and 3 women with a median age of 50 years (range 23-74), median Charlson Comorbidity Score of 2 (range 0-7), and median Acute Physiology and Chronic Health Evaluation Score of 13 (range 5-33) at the time of IVIG. The IVIG total dose ranged from 0.5 to 2.0 g/kg (median 1.25 g/kg) distributed over 1-4 daily doses. The most common regimen received was 0.5 g/kg daily for 3 days. The median time to IVIG administration was 9 days (range 0-48 days) after admission. The median time from first IVIG dose administration to hospital discharge was 14 days (range 3-48). The 5 patients who received IVIG ≤4 days of admission demonstrated a significantly shorter length of hospital stay after treatment (median 7 days, range 3-14 days) than the 7 patients who received it >7 days after admission (median 33 days, range 8-48 days, p = 0.03, Mann-Whitney U test). These cases demonstrate that IVIG may improve the clinical state of patients with moderate to severe COVID-19 infection. Despite very high illness severity scores, all patients survived hospital discharge. No thrombotic events occurred and IVIG was well tolerated, despite most cases demonstrating very elevated D-dimer suggestive of active intravascular fibrinolysis. We believe that IVIG warrants immediate clinical trial evaluation in COVID-19 to confirm its role as a mainstay treatment of moderate to severe COVID-19 infection as a means to reduce hospital stay and utilization of ICU resources, including mechanical ventilation, and potentially reduce mortality.


Asunto(s)
/terapia , Oxigenación por Membrana Extracorpórea , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Unidades de Cuidados Intensivos , Tiempo de Internación , Respiración Artificial , APACHE , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Anciano , Alanina/análogos & derivados , Alanina/uso terapéutico , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Doxiciclina/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
17.
Can Respir J ; 2020: 4312519, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33082891

RESUMEN

Background: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in an unprecedented public health challenge worldwide. Despite urgent and extensive global efforts, the existing evidence is inconclusive regarding the medications used for the treatment of COVID-19. Purpose: To generate an up-to-date evidence for the clinical safety and efficacy of hydroxychloroquine (HCQ) with or without azithromycin (AZ) among patients treated for COVID-19. Data Source. PubMed, Cochrane CENTRAL, LITCOVID, Web of Science, SCOPUS, BioRxiv, Embase, MedRxiv, and Wiley online library were searched from 2019/12/30 to 2020/05/23. Study Selection. Three investigators assessed the quality of the studies. Data Extraction. Data about study characteristics, effect estimates, and the quality of the studies were extracted by two independent reviewers and cross-checked by the third reviewer. Data Synthesis. The data of 6,782 (HCQ group, 3623; HCQ + AZ group, 1,020; control group, 2139) participants were included. HCQ was compared with standard care for virologic efficacy, disease progression, mortality, and adverse effects. HCQ was also compared with HCQ + AZ for QTc prolongation, admission to the intensive care unit, and mortality. The study found HCQ did not alter the rate of virologic cure (OR = 0.78; 95% CI: 0.39-1.56) and the risk of mortality (OR = 1.26; 95% CI: 0.66-2.39). The pooled prevalence for mortality was 5.8% (95% CI: 0.9%-10.8%). Moreover, HCQ did not impact disease progression (OR = 0.9; 95% CI: 0.36-2.29) but resulted in a higher risk of adverse effects (OR = 2.35; 95% CI: 1.15-4.8). HCQ was also compared against HCQ + AZ, and no difference was observed in QTc prolongation above 500 ms (OR = 1.11; 95% CI: 0.54-2.28), admission to the intensive care unit (OR = 0.92; 95% CI: 0.52-1.63), and mortality (OR = 0.88; 95% CI: 0.55-1.43). However, in the analysis of single-arm studies, about 11.2% (95% CI: 7.0%-15.5%) of patients have developed an absolute increase of QTc greater than 500 ms, and 4.1% (95% CI: 1.1%-7.1%) of patients discontinued their medication. Conclusion: This meta-analysis and systematic review, which included a limited number of poorly designed studies of patients with COVID-19, revealed HCQ is intolerable, unsafe, and not efficacious. Similarly, HCQ + AZ combination was not different from HCQ alone in curbing mortality and ICU admission.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Hidroxicloroquina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Humanos , Pandemias
18.
Eur Rev Med Pharmacol Sci ; 24(18): 9744-9747, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33015820

RESUMEN

OBJECTIVE: ACE2 long served as the human gateway for multiple coronaviruses, including the currently pandemic SARS-CoV-2. This mini-review explores the potential of targeting ACE2 in blocking viral penetrance. MATERIALS AND METHODS: PubMed search was conducted using the terms: "coronaviridae", "peptidyl-dipeptidase A", "ACE2", "SARS", and "SARS-CoV-2". References of relevant articles were further screened by the author. RESULTS: Four main methods of blocking ACE2-mediated viral penetrance were identified: receptor blockage, receptor decoying, receptor shedding, and co-receptor inhibition. CONCLUSIONS: Drugs that inhibit viral binding to ACE2 present a strong choice for the current, and if necessary, future outbreaks. Further research is needed to establish the clinical and pharmacological aspects of the identified candidate molecules.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Terapia Molecular Dirigida/métodos , Peptidil-Dipeptidasa A/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Humanos , Pandemias
19.
Trials ; 21(1): 754, 2020 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-32867852

RESUMEN

OBJECTIVES: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. PARTICIPANTS: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded. INTERVENTION AND COMPARATOR: The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group). MAIN OUTCOMES: Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events. RANDOMISATION: Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW - nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation BLINDING (MASKING): This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms. TRIAL STATUS: HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Asunto(s)
Infecciones por Coronavirus/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Personal de Salud , Hidroxicloroquina/uso terapéutico , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Enfermedades Profesionales/prevención & control , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Betacoronavirus , Quimioprevención , Infecciones por Coronavirus/transmisión , Humanos , India , Neumonía Viral/transmisión
20.
Medicine (Baltimore) ; 99(33): e21121, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32871981

RESUMEN

BACKGROUD: Mycophenolate mofetil (MMF) has been recommended for the treatment of lupus nephritis (LN). Although inter-racial differences exist regarding the appropriate dose and efficacy of MMF in patients with LN, no definitive meta-analysis has yet been conducted in Chinese patients. This analysis investigated the efficacy and safety of MMF in Chinese patients with proliferative LN. METHODS: A systematic literature search was conducted to select randomized controlled trials that reported at least one of the following: complete remission (CR), partial remission, total remission (TR; defined as complete remission + partial remission), relapse rate, serum creatinine, creatinine clearance, end-stage renal disease, death, infections, amenorrhea, leukopenia, alopecia, gastrointestinal symptoms, or liver damage. RESULTS: Eighteen trials (927 patients) were included; 14 (750 patients) reported CR, partial remission, and TR. Two trials (58 patients) reported relapse rates during maintenance treatment. MMF induction significantly improved CR and TR vs cyclophosphamide (relative risk 1.34, 95% confidence interval: 1.13-1.58; P < .001; relative risk 1.16, 95% confidence interval: 1.02-1.33; P = .03), and was associated with significantly lower risks of infection (P < .001), amenorrhea (P < .001), leukopenia, and alopecia. No significant difference in relapse rate was evident between the MMF and azathioprine groups (P = .66). CONCLUSION: According to this meta-analysis of 18 trials, MMF is significantly more effective than cyclophosphamide induction, and is associated with reduced incidences of infections, amenorrhea, leukopenia, and alopecia in Chinese patients with proliferative LN.


Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/etnología , Ácido Micofenólico/uso terapéutico , Grupo de Ascendencia Continental Asiática , China , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Inhibidores Enzimáticos/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Ácido Micofenólico/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
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