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1.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576241

RESUMO

Although it had been reported that Israeli acute paralysis virus (IAPV) can cause systemic infection in honey bees, little is known about how it establishes this infection and results in the typical symptoms, paralysis and trembling. Here, we used our previously constructed IAPV infectious clone to investigate viral loads in different tissues of honey bees and further identify the relation between tissue tropism and paralytic symptoms. Our results showed that tracheae showed a greater concentration of viral abundance than other tissues. The abundance of viral protein in the tracheae was positively associated with viral titers, and was further confirmed by immunological and ultrastructural evidence. Furthermore, higher viral loads in tracheae induced remarkable down-regulation of succinate dehydrogenase and cytochrome c oxidase genes, and progressed to causing respiratory failure of honey bees, resulting in the appearance of typical symptoms, paralysis and body trembling. Our results showed that paralysis symptoms or trembling was actually to mitigate tachypnea induced by IAPV infection due to the impairment of honey bee tracheae, and revealed a direct causal link between paralysis symptoms and tissue tropism. These findings provide new insights into the understanding of the underlying mechanism of paralysis symptoms of honey bees after viral infection and have implications for viral disease prevention and specific therapeutics in practice.


Assuntos
Dicistroviridae , Paralisia/fisiopatologia , Taquipneia/fisiopatologia , Viroses/fisiopatologia , Animais , Abelhas/virologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Paralisia/virologia , Succinato Desidrogenase/metabolismo , Taquipneia/virologia , Traqueia/virologia , Carga Viral , Proteínas Virais , Viroses/virologia
3.
PLoS One ; 16(6): e0252411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34143791

RESUMO

BACKGROUND: In order for healthcare systems to prepare for future waves of COVID-19, an in-depth understanding of clinical predictors is essential for efficient triage of hospitalized patients. METHODS: We performed a retrospective cohort study of 259 patients admitted to our hospitals in Rhode Island to examine differences in baseline characteristics (demographics and comorbidities) as well as presenting symptoms, signs, labs, and imaging findings that predicted disease progression and in-hospital mortality. RESULTS: Patients with severe COVID-19 were more likely to be older (p = 0.02), Black (47.2% vs. 32.0%, p = 0.04), admitted from a nursing facility (33.0% vs. 17.9%, p = 0.006), have diabetes (53.9% vs. 30.4%, p<0.001), or have COPD (15.4% vs. 6.6%, p = 0.02). In multivariate regression, Black race (adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI]: 1.1-3.9) and diabetes (aOR 2.2, 95%CI: 1.3-3.9) were independent predictors of severe disease, while older age (aOR 1.04, 95% CI: 1.01-1.07), admission from a nursing facility (aOR 2.7, 95% CI 1.1-6.7), and hematological co-morbidities predicted mortality (aOR 3.4, 95% CI 1.1-10.0). In the first 24 hours, respiratory symptoms (aOR 7.0, 95% CI: 1.4-34.1), hypoxia (aOR 19.9, 95% CI: 2.6-152.5), and hypotension (aOR 2.7, 95% CI) predicted progression to severe disease, while tachypnea (aOR 8.7, 95% CI: 1.1-71.7) and hypotension (aOR 9.0, 95% CI: 3.1-26.1) were associated with increased in-hospital mortality. CONCLUSIONS: Certain patient characteristics and clinical features can help clinicians with early identification and triage of high-risk patients during subsequent waves of COVID-19.


Assuntos
COVID-19/epidemiologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Idoso , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Diabetes Mellitus/epidemiologia , Epidemias , Feminino , Humanos , Hipotensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rhode Island/epidemiologia , Fatores de Risco , SARS-CoV-2/fisiologia , Taquipneia/epidemiologia , Triagem/métodos
5.
J Med Virol ; 93(9): 5452-5457, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33969515

RESUMO

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.


Assuntos
COVID-19/patologia , Creatina Quinase/sangue , Magnésio/sangue , RNA Viral/sangue , SARS-CoV-2/patogenicidade , Viremia/patologia , Adolescente , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Criança , Pré-Escolar , Tosse/diagnóstico , Tosse/mortalidade , Tosse/patologia , Tosse/virologia , Feminino , Febre/diagnóstico , Febre/mortalidade , Febre/patologia , Febre/virologia , Hospitais , Humanos , Lactente , Recém-Nascido , Irã (Geográfico) , Masculino , RNA Viral/genética , SARS-CoV-2/genética , Índice de Gravidade de Doença , Análise de Sobrevida , Taquipneia/diagnóstico , Taquipneia/mortalidade , Taquipneia/patologia , Taquipneia/virologia , Viremia/diagnóstico , Viremia/mortalidade , Viremia/virologia
6.
Am J Emerg Med ; 48: 376.e1-376.e2, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33958247

RESUMO

The pediatric population accounts for a small portion of those with severe disease related to COVID-19. There are few published reports of hypercoagulable states in children with COVID-19. We describe an 11-year-old male with nephrotic syndrome who required inpatient treatment for COVID-19 pneumonia eight weeks prior. He returned to the emergency department with vomiting, tachypnea and was found to have a pulmonary embolism. In this case report, we discuss the risk factors for, presentation and evaluation of hypercoagulable state and its relation to COVID-19 in a pediatric patient.


Assuntos
COVID-19/sangue , Síndrome Nefrótica/complicações , Embolia Pulmonar/diagnóstico , Doença Cardiopulmonar/diagnóstico , Trombofilia/sangue , COVID-19/complicações , Criança , Angiografia por Tomografia Computadorizada , Eletrocardiografia , Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Hospitalização , Humanos , Unidades de Terapia Intensiva Pediátrica , Masculino , Readmissão do Paciente , Obesidade Pediátrica/complicações , Embolia Pulmonar/sangue , Embolia Pulmonar/complicações , Embolia Pulmonar/tratamento farmacológico , Doença Cardiopulmonar/tratamento farmacológico , Doença Cardiopulmonar/etiologia , SARS-CoV-2 , Taquipneia , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Vômito
7.
J Appl Physiol (1985) ; 130(5): 1436-1447, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33661723

RESUMO

Newborn infants with respiratory difficulties frequently require nasal respiratory support such as nasal continuous positive airway pressure (nCPAP) or high-flow nasal cannulae (HFNC). Oral feeding of these infants under nasal respiratory support remains controversial out of fear of aspiration and cardiorespiratory events. The main objective of this study was to evaluate the safety of oral feeding under different types of nasal respiratory support in newborn lambs without or with tachypnea. Eight lambs aged 4-5 days were instrumented to record sucking, swallowing, respiration, ECG, oxygen saturation, and arterial blood gases. Each lamb was given two bottles of 30 mL of milk with a pause of 30 s under videofluoroscopy in four conditions [no respiratory support, nCPAP 6 cmH2O, HFNC 7 L/min, HFNCCPAP (= HFNC 7 L/min + CPAP 6 cmH2O)] administered in random order. The study was conducted in random order over 2 days, with or without standardized tachypnea induced by thoracic compression with a blood pressure cuff. Generalized linear mixed models were used to compare the four nasal respiratory supports in terms of safety (cardiorespiratory events and aspiration), sucking-swallowing-breathing coordination, and efficacy of oral feeding. Results reveal that no nasal respiratory support impaired the safety of oral feeding. Most of the few laryngeal penetrations we observed occurred with HFNCCPAP. Nasal CPAP modified sucking-swallowing-breathing coordination, whereas the efficiency of oral feeding decreased under HFNCCPAP. Results were similar with or without tachypnea. In conclusion, oral feeding under nasal respiratory support is generally safe in a term lamb, even with tachypnea.NEW & NOTEWORTHY The practice of orally feeding newborns suffering from respiratory problems while on nCPAP or HFNC remains controversial for fear of triggering cardiorespiratory events or aspiration pneumonia, or aggravating chronic lung disease. The present results show that bottle-feeding is generally safe in full-term lambs under nasal respiratory support, both without and with tachypnea.


Assuntos
Alimentação Artificial , Pressão Positiva Contínua nas Vias Aéreas , Animais , Animais Recém-Nascidos , Humanos , Lactente , Oxigenoterapia , Respiração , Ovinos , Taquipneia
8.
Pediatr Rheumatol Online J ; 19(1): 29, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726806

RESUMO

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.


Assuntos
COVID-19/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Hipotensão/fisiopatologia , Linfopenia/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Miocardite/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Distribuição por Idade , Antirreumáticos/uso terapêutico , Aspirina/uso terapêutico , Proteína C-Reativa/metabolismo , COVID-19/epidemiologia , COVID-19/metabolismo , COVID-19/terapia , Criança , Pré-Escolar , Tosse/fisiopatologia , Diarreia/fisiopatologia , Dispneia/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hiperferritinemia/metabolismo , Hiperferritinemia/fisiopatologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lactente , Unidades de Terapia Intensiva Pediátrica , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Itália/epidemiologia , Masculino , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/terapia , Inibidores da Agregação Plaquetária/uso terapêutico , SARS-CoV-2 , Choque/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/terapia , Taquipneia/fisiopatologia , Troponina T/metabolismo , Vômito/fisiopatologia
9.
JAMA Netw Open ; 4(3): e211085, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688964

RESUMO

Importance: Solid estimates of the risk of developing symptoms and of progressing to critical disease in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are key to interpreting coronavirus disease 2019 (COVID-19) dynamics, identifying the settings and the segments of the population where transmission is more likely to remain undetected, and defining effective control strategies. Objective: To estimate the association of age with the likelihood of developing symptoms and the association of age with the likelihood of progressing to critical illness after SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study analyzed quarantined case contacts, identified between February 20 and April 16, 2020, in the Lombardy region of Italy. Contacts were monitored daily for symptoms and tested for SARS-CoV-2 infection, by either real-time reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs or retrospectively via IgG serological assays. Close contacts of individuals with laboratory-confirmed COVID-19 were selected as those belonging to clusters (ie, groups of contacts associated with an index case) where all individuals were followed up for symptoms and tested for SARS-CoV-2 infection. Data were analyzed from February to June 2020. Exposure: Close contact with individuals with confirmed COVID-19 cases as identified by contact tracing operations. Main Outcomes and Measures: Age-specific estimates of the risk of developing respiratory symptoms or fever greater than or equal to 37.5 °C and of experiencing critical disease (defined as requiring intensive care or resulting in death) in SARS-CoV-2-infected case contacts. Results: In total, 5484 case contacts (median [interquartile range] age, 50 [30-61] years; 3086 female contacts [56.3%]) were analyzed, 2824 of whom (51.5%) tested positive for SARS-CoV-2 (median [interquartile range] age, 53 [34-64] years; 1604 female contacts [56.8%]). The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older. Most infected contacts (1948 of 2824 individuals [69.0%]) did not develop respiratory symptoms or fever greater than or equal to 37.5 °C. Only 26.1% (95% CI, 24.1%-28.2%) of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5 °C; among infected participants older than 60 years, 6.6% (95% CI, 5.1%-8.3%) developed critical disease. Female patients were 52.7% (95% CI, 24.4%-70.7%) less likely than male patients to develop critical disease after SARS-CoV-2 infection. Conclusions and Relevance: In this Italian cohort study of close contacts of patients with confirmed SARS-CoV-2 infection, more than one-half of individuals tested positive for the virus. However, most infected individuals did not develop respiratory symptoms or fever. The low proportion of children and young adults who developed symptoms highlights the possible challenges in readily identifying SARS-CoV-2 infections.


Assuntos
COVID-19/fisiopatologia , Portador Sadio/epidemiologia , Tosse/epidemiologia , Dispneia/epidemiologia , Febre/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Dor no Peito/epidemiologia , Dor no Peito/fisiopatologia , Criança , Pré-Escolar , Busca de Comunicante , Tosse/fisiopatologia , Estado Terminal , Progressão da Doença , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Faringite/epidemiologia , Faringite/fisiopatologia , Quarentena , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Taquipneia/epidemiologia , Taquipneia/fisiopatologia , Adulto Jovem
11.
Hipertens. riesgo vasc ; 38(1): 44-47, ene.-mar. 2021. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-202412

RESUMO

Presentamos el caso de un paciente de 34 años que sufre un traumatismo craneoencefálico grave con afectación cerebral severa. Evoluciona de manera tórpida precisando varias reintervenciones por sangrado y herniación de masa encefálica. Nos interconsultan desde Neurocirugía por irregular control de cifras de presión arterial a pesar de tratamiento con calcioantagonistas. El paciente asocia diaforesis, taquipnea y taquicardia, junto a fiebre de alto grado de forma persistente sin evidencia microbiológica. Analítica con función renal normal, sin proteinuria y sin datos de hipertrofia de ventrículo izquierdo que sugieran hipertensión arterial previa. Esto nos hace plantearnos como primera posibilidad diagnóstica un síndrome de hiperactividad simpática debido al daño neurológico severo. Se inicia terapia antihipertensiva orientada a esta sospecha, entre los que se incluyen betabloqueantes no cardioselectivos, alfa-2-agonistas, benzodiacepinas y agonistas de los receptores GABA. Así se consigue mejorar la labilidad de las cifras de presión arterial, lo que apoya el diagnóstico


We present the case of a 34-year-old patient with severe head trauma and severe brain involvement. The patient deteriorated progressively and required several reinterventions for bleeding and brain herniation. We were consulted by neurosurgery due to irregular blood pressure control despite treatment with calcium antagonists. The patient had associated diaphoresis, tachypnoea and tachycardia, together with persistent high-grade fever with no microbiological evidence. Laboratory tests showed normal kidney function, with no proteinuria and no signs of left ventricular hypertrophy to suggest previous arterial hypertension. This led us to consider sympathetic hyperactivity syndrome as a first possible diagnosis due to severe neurological damage. In line with this suspicion, antihypertensive therapy was initiated which included non-cardioselective beta-blockers, alpha-2 agonists, benzodiazepines and GABA receptor agonists. Thus, we were able to improve the labile blood pressure levels, which supports the diagnosis


Assuntos
Humanos , Masculino , Adulto , Traumatismos Cranianos Penetrantes/complicações , Hipertensão/etiologia , Pressão Arterial/efeitos dos fármacos , Hematoma Epidural Craniano/diagnóstico por imagem , Sistema Nervoso Simpático/fisiopatologia , Lesões Encefálicas/complicações , Traumatismos Cranianos Penetrantes/cirurgia , Taquipneia/complicações , Taquicardia/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Anti-Hipertensivos/uso terapêutico , Doenças do Sistema Nervoso Central/etiologia
13.
Trials ; 22(1): 42, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430924

RESUMO

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in 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.


Assuntos
COVID-19/tratamento farmacológico , Ecdisterona/uso terapêutico , Insuficiência Respiratória/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Hospitalização , Humanos , Hipóxia/fisiopatologia , Pessoa de Meia-Idade , Mortalidade , Oxigenoterapia/estatística & dados numéricos , Proteínas Proto-Oncogênicas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Coronavírus/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/fisiopatologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Taquipneia/fisiopatologia , Resultado do Tratamento
14.
Internist (Berl) ; 62(6): 672-678, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-33411015

RESUMO

Patients with type 2 diabetes who present with confusion and/or abdominal pains should be screened for sodium-glucose cotransporter 2 (SGLT-2)-induced diabetic ketoacidosis. Severe acidosis was diagnosed despite only moderately increased blood sugar levels. If so, immediate ICU treatment is essential.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/terapia , Humanos , Hipoglicemiantes , Masculino , Taquicardia , Taquipneia
15.
Brain Dev ; 43(2): 230-233, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33082059

RESUMO

BACKGROUND: Reversible splenial lesion syndrome (RESLES) is characterized by a temporary lesion in the splenium of the corpus callosum, emerging related to encephalitis, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Among RESLES, mild encephalitis/encephalopathy with reversible splenial lesion (MERS) has been defined as a distinct clinicoradiologic syndrome associated with viral infections. CASE PRESENTATION: We report two children with multisystem inflammatory syndrome-children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who developed RESLES during the disease course. Encephalopathy was the main central nervous system symptom. Both of the children showed a rapid recovery, and brain magnetic resonance imaging revealed complete resolution of the splenial lesion within 1 week. CONCLUSION: The complete resolution of the splenial lesion and rapid recovery from encephalopathy in RESLES associated with SARS CoV-2 were similar to observed in MERS.


Assuntos
Encefalopatias/diagnóstico por imagem , COVID-19/diagnóstico , Corpo Caloso/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Encefalopatias/tratamento farmacológico , Encefalopatias/fisiopatologia , COVID-19/diagnóstico por imagem , COVID-19/tratamento farmacológico , COVID-19/fisiopatologia , Criança , Dispneia/fisiopatologia , Eletroencefalografia , Exantema/fisiopatologia , Feminino , Febre/fisiopatologia , Glucocorticoides/uso terapêutico , Alucinações/fisiopatologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Metilprednisolona/uso terapêutico , Transtornos Neurocognitivos/diagnóstico por imagem , Transtornos Neurocognitivos/fisiopatologia , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Taquipneia/fisiopatologia
16.
Cardiol Young ; 31(3): 485-487, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33118485

RESUMO

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.


Assuntos
COVID-19/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Diarreia/fisiopatologia , Febre/fisiopatologia , Taquicardia/fisiopatologia , Taquipneia/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Vômito/fisiopatologia , COVID-19/complicações , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/metabolismo , Cardiotônicos/uso terapêutico , Diuréticos/uso terapêutico , Ecocardiografia , Infecções por Enterovirus/complicações , Feminino , Frequência Cardíaca , Transplante de Coração , Humanos , Lactente , Milrinona/uso terapêutico , Miocardite/complicações , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , SARS-CoV-2 , Índice de Gravidade de Doença , Troponina T/metabolismo , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Listas de Espera , Equilíbrio Hidroeletrolítico
17.
Am J Emerg Med ; 46: 449-455, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33176953

RESUMO

OBJECTIVES: To describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4). METHODS: We conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines. RESULTS: A total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p < .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20-4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31-0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38-0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38-0.82]), hypoxemia (OR, 0.34 [0.18-0.64]), or increased heart (OR 0.83 [0.73-0.95]) or respiratory (OR 0.70 [0.60-0.82]) rates. CONCLUSION: Patients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage.


Assuntos
Anafilaxia/diagnóstico , Serviço Hospitalar de Emergência , Gravidade do Paciente , Tempo para o Tratamento/estatística & dados numéricos , Triagem , Centros Médicos Acadêmicos , Adolescente , Adulto , Fatores Etários , Anafilaxia/tratamento farmacológico , Anafilaxia/fisiopatologia , Angioedema/fisiopatologia , Criança , Pré-Escolar , Estudos de Coortes , Serviços Médicos de Emergência , Epinefrina/uso terapêutico , Feminino , Humanos , Hipóxia/fisiopatologia , Lactente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Faringe , Prurido/fisiopatologia , Índice de Gravidade de Doença , Simpatomiméticos/uso terapêutico , Taquicardia/fisiopatologia , Taquipneia/fisiopatologia , Urticária/fisiopatologia , Úvula , Adulto Jovem
18.
Pulmonology ; 27(1): 35-42, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32127307

RESUMO

BACKGROUND AND OBJECTIVES: Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. METHODS: This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). RESULTS: Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. CONCLUSIONS: The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.


Assuntos
Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Projetos de Pesquisa/normas , Tuberculose Pulmonar/mortalidade , Estudos de Casos e Controles , Serviço Hospitalar de Emergência , Feminino , Hospitalização/tendências , Humanos , Hipotensão/complicações , Hipotensão/mortalidade , Hipóxia/complicações , Hipóxia/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Radiografia Torácica/métodos , Fatores de Risco , Índice de Gravidade de Doença , Taquicardia/complicações , Taquicardia/mortalidade , Taquipneia/complicações , Taquipneia/mortalidade , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/reabilitação
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