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3.
Cells ; 10(10)2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34685567

RESUMO

Mesenchymal stem cells (MSCs) are multipotent adult stem cells present in virtually all tissues; they have a potent self-renewal capacity and can differentiate into multiple cell types. They also affect the ambient tissue by the paracrine secretion of numerous factors in vivo, including the induction of other stem cells' differentiation. In vitro, the culture media supernatant is named secretome and contains soluble molecules and extracellular vesicles that retain potent biological function in tissue regeneration. MSCs are considered safe for human treatment; their use does not involve ethical issues, as embryonic stem cells do not require genetic manipulation as induced pluripotent stem cells, and after intravenous injection, they are mainly found in the lugs. Therefore, these cells are currently being tested in various preclinical and clinical trials for several diseases, including COVID-19. Several affected COVID-19 patients develop induced acute respiratory distress syndrome (ARDS) associated with an uncontrolled inflammatory response. This condition causes extensive damage to the lungs and may leave serious post-COVID-19 sequelae. As the disease may cause systemic alterations, such as thromboembolism and compromised renal and cardiac function, the intravenous injection of MSCs may be a therapeutic alternative against multiple pathological manifestations. In this work, we reviewed the literature about MSCs biology, focusing on their function in pulmonary regeneration and their use in COVID-19 treatment.


Assuntos
COVID-19/sangue , COVID-19/terapia , Pulmão/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Regeneração/fisiologia , Animais , COVID-19/tratamento farmacológico , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Meios de Cultura , Vesículas Extracelulares , Humanos , Inflamação , Camundongos , Camundongos SCID , Fenótipo , Pneumonia/sangue , Pneumonia/imunologia , Pneumonia/terapia , Síndrome do Desconforto Respiratório , SARS-CoV-2 , Tromboembolia/sangue , Tromboembolia/imunologia , Tromboembolia/terapia
4.
J Glob Health ; 11: 04053, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552722

RESUMO

Background: With an estimated 1 million cases per year, pneumonia accounts for 15% of all under-five deaths globally, and hypoxaemia is one of the strongest predictors of mortality. Most of these deaths are preventable and occur in low- and middle-income countries. Bangladesh is among the six high burden countries with an estimated 4 million pneumonia episodes annually. There is a gap in updated evidence on the prevalence of hypoxaemia among children with severe pneumonia in high burden countries, including Bangladesh. Methods: We conducted a secondary analysis of data obtained from icddr,b-Dhaka Hospital, a secondary level referral hospital located in Dhaka, Bangladesh. We included 2646 children aged 2-59 months admitted with WHO-defined severe pneumonia during 2014-17. The primary outcome of interest was hypoxaemia, defined as SpO2 < 90% on admission. The secondary outcome of interest was adverse clinical outcomes defined as deaths during hospital stay or referral to higher-level facilities due to clinical deterioration. Results: On admission, the prevalence of hypoxaemia among children hospitalised with severe pneumonia was 40%. The odds of hypoxaemia were higher among females (adjusted Odds ratio AOR = 1.44; 95% confidence interval CI = 1.22-1.71) and those with a history of cough or difficulty in breathing for 0-48 hours before admission (AOR = 1.61; 95% CI = 1.28-2.02). Among all children with severe pneumonia, 6% died during the hospital stay, and 9% were referred to higher-level facilities due to clinical deterioration. Hypoxaemia was the strongest predictor of mortality (AOR = 11.08; 95% CI = 7.28-16.87) and referral (AOR = 5.94; 95% CI = 4.31-17) among other factors such as age, sex, history of fever and cough or difficulty in breathing, and severe acute malnutrition. Among those who survived, the median duration of hospital stay was 7 (IQR = 4-11) days in the hypoxaemic group and 6 (IQR = 4-9) days in the non-hypoxaemic group, and the difference was significant at P < 0.001. Conclusions: The high burden of hypoxaemia and its clinical outcomes call for urgent attention to promote oxygen security in low resource settings like Bangladesh. The availability of pulse oximetry for rapid identification and an effective oxygen delivery system for immediate correction should be ensured for averting many preventable deaths.


Assuntos
Pneumonia , Bangladesh/epidemiologia , Criança , Feminino , Humanos , Hipóxia/epidemiologia , Hipóxia/terapia , Lactente , Pneumonia/epidemiologia , Pneumonia/terapia , Prevalência , Organização Mundial da Saúde
5.
Ann Clin Microbiol Antimicrob ; 20(1): 69, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563202

RESUMO

BACKGROUND: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. METHODS: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. RESULTS: Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. CONCLUSIONS: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. TRIAL REGISTRATION: Not applicable as this was a retrospective chart review study without interventional arm.


Assuntos
Bactérias/efeitos dos fármacos , Infecções Bacterianas/complicações , COVID-19/terapia , Infecção Hospitalar/complicações , Fungos/efeitos dos fármacos , Micoses/complicações , Pneumonia/terapia , Escarro/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos , Anti-Infecciosos/farmacologia , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Farmacorresistência Fúngica Múltipla , Feminino , Fungos/genética , Fungos/isolamento & purificação , Hospitalização , Humanos , Intubação , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Pneumonia/complicações , Pneumonia/mortalidade , Pneumonia/virologia , Estudos Retrospectivos , SARS-CoV-2/fisiologia
6.
J Intensive Care Med ; 36(10): 1228-1232, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34516306

RESUMO

We present 2 patients with rapidly escalating oxygen requirements from severe acute respiratory syndrome coronavirus 2 infection (COVID-19) treated with the Seraph100 Microbind Affinity Blood Filter under Emergency Use Authorization from the US Federal Drug Administration. The Seraph100 is an extracorporeal hemoperfusion filter previously demonstrated to remove viral particles and pro-inflammatory cytokines from the blood. Treatment with the Seraph100 filter was associated with a rapid improvement in oxygenation and both patients were discharged from the hospital without supplemental oxygen.


Assuntos
COVID-19 , Hemoperfusão , Pneumonia , Humanos , Pulmão , Pneumonia/terapia , SARS-CoV-2
7.
Front Immunol ; 12: 709861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475873

RESUMO

Background: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. Methods: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. Results: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. Conclusions: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.


Assuntos
Anticorpos Monoclonais/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Pneumonia/terapia , Administração Intranasal , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Biomarcadores , Proteína C-Reativa/análise , COVID-19/fisiopatologia , COVID-19/terapia , Estudos de Coortes , Feminino , Humanos , Imunidade/efeitos dos fármacos , Interleucina-6/sangue , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Projetos Piloto , Pneumonia/prevenção & controle , Adulto Jovem
8.
Respir Investig ; 59(6): 748-756, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34481816

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a valuable rescue therapy to treat refractory hypoxemia caused by influenza. The present meta-analysis aimed to compare the clinical characteristics and outcomes of ECMO between COVID-19 and influenza. METHODS: We searched the PubMed, Cochrane Library, SCOPUS, and Web of Science databases from inception to May 1, 2021. The included studies compared the clinical characteristics and outcomes of ECMO between adults with COVID-19 and those with influenza. RESULTS: The study included four retrospective cohorts involving a total of 129 patients with COVID-19 and 140 with influenza who were treated using ECMO. Clinical characteristics were similar between the COVID-19 and influenza groups, including body mass index (BMI), diabetes mellitus, hypertension, and immunocompromised status. A higher proportion of patients with COVID-19 on ECMO were male (75.9% vs. 62.9%; P = 0.04). There was no difference between the groups in terms of illness severity based on sequential organ failure assessment (SOFA) score or serum pH. Patients with COVID-19 had a longer mean duration of mechanical ventilation before ECMO (6.63 vs. 3.38 days; P < 0.01). The pooled mortality rate was 43.8%. The mean ECMO duration (14.13 vs. 12.55 days; P = 0.25) and mortality rate (42.6% vs. 45.0%; P = 0.99) were comparable between the groups. CONCLUSION: Clinical characteristics, ECMO duration, and mortality were comparable between patients with COVID-19 and those with influenza who required ECMO to treat refractory hypoxemia. The duration of mechanical ventilation before ECMO did not influence outcomes. Patients with COVID-19 benefit from ECMO salvage therapy similarly to those with influenza.


Assuntos
COVID-19/complicações , Oxigenação por Membrana Extracorpórea/efeitos adversos , Influenza Humana/complicações , Pneumonia/terapia , Síndrome do Desconforto Respiratório/terapia , COVID-19/terapia , Humanos , Influenza Humana/terapia , Unidades de Terapia Intensiva , Pandemias , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , Resultado do Tratamento
9.
PLoS One ; 16(9): e0256856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34469441

RESUMO

BACKGROUND: Pneumonia is a significant cause of morbidity and mortality among adults globally. This retrospective cohort analysis assessed the pneumonia burden and related healthcare resource utilization and costs in the at-risk (low, medium, and high-risk) adult patients in Dubai, United Arab Emirates (UAE). METHODS: The claims data from January 1, 2014 to June 30, 2019 were extracted from the Dubai Real-World Claims Database for patients, aged ≥18 year, having at least 1 pneumonia claim. Data for the inpatient, outpatient and emergency visits were assessed for 12-months, before (pre-index) and after (follow-up) a pneumonia episode. Healthcare costs were calculated based on dollar value of 2020. RESULTS: Total 48,562 records of eligible patients were analyzed (mean age = 39.9 years; low [62.1%], medium [36.2%] and high [1.7%] risk cohorts). Mean all-cause healthcare costs were approximately >45% higher in the follow-up period (1,947 USD/patient) versus pre-index period (1,327 USD/patient). During follow-up period, the mean annual pneumonia incidence rate was 1.3 episodes, with a similar pattern across all cohorts. Overall, mean claims and costs (USD) per patient (all-cause) were highest in the high-risk cohort in the follow-up period (claims: overall, 11.6; high-risk, 22.0; medium-risk, 13.9; low-risk, 9.9; costs: high-risk, 14,184; medium-risk, 2,240; low-risk, 1,388). Similarly, the mean pneumonia-related costs (USD) per patient were highest for the high-risk cohort (overall: 1,305; high-risk, 10,207; medium-risk, 1,283; low-risk, 882), however, the claims were similar across cohorts (claims/patient: overall: 2.0; high-risk, 1.9; medium-risk, 2.2; low-risk, 1.9). Most all-cause and pneumonia-related costs were due to inpatient visits (4,901 and 4,818 USD respectively), while outpatient (1,232 and 166 USD respectively) and emergency visits (347 and 206 USD respectively) contributed significantly lesser. CONCLUSIONS: Pneumonia imposes a significant healthcare burden in the UAE, especially in the high-risk patients with severe comorbidities. These findings would guide clinicians and policy makers to make informed decisions.


Assuntos
Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pneumonia/economia , Adolescente , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/terapia , Estudos Retrospectivos , Emirados Árabes Unidos/epidemiologia , Adulto Jovem
10.
Geriatr Gerontol Int ; 21(10): 926-931, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34390116

RESUMO

AIM: This study aimed to assess the association between physical frailty and clinical outcomes among older patients hospitalized for pneumonia. METHODS: This study examined 852 consecutive patients hospitalized for pneumonia between October 2018 and September 2020. Patients who were <65 years old, scheduled for admission, did not receive inpatient rehabilitation, or died during admission were excluded. A short physical performance battery (SPPB) test was performed by physical therapists upon discharge. The primary outcome measure was a composite endpoint of readmission or mortality due to any cause within 6 months of discharge. RESULTS: In total, 521 patients (median age, 80 years; interquartile range, 74-86 years) were included in the analyses, and were divided into the following two groups: robust group with SPPB scores >9 (n = 150), and physical frailty group with SPPB scores ≤9 (n = 371). Of these, 346 (66.4%) patients were men; and the median SPPB score was 6 (interquartile range, 1-10). During the median follow-up period of 53 days (interquartile range, 4-180 days), 92 (17.6%) patients were readmitted and 25 (4.8%) patients died. Patients with physical frailty were at an increased risk for the primary endpoint (hazard ratio, 2.21; 95% confidence interval, 1.44-3.41; P < 0.001); the risk remained significant after adjusting for multiple variables (adjusted hazard ratio, 1.70; 95% confidence interval, 1.05-2.74; P = 0.028). CONCLUSIONS: Among older patients with pneumonia, physical frailty status at discharge was an independent risk factor for readmission and mortality within 6 months after initial discharge. Geriatr Gerontol Int 2021; 21: 926-931.


Assuntos
Fragilidade , Pneumonia , Idoso , Idoso de 80 Anos ou mais , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Hospitalização , Humanos , Masculino , Alta do Paciente , Pneumonia/epidemiologia , Pneumonia/terapia
11.
Int J Infect Dis ; 111: 108-116, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34416403

RESUMO

OBJECTIVES: To validate and recalibrate the CURB-65 and pneumonia severity index (PSI) in predicting 30-day mortality and critical care intervention (CCI) in a multiethnic population with COVID-19, along with evaluating both models in predicting CCI. METHODS: Retrospective data was collected for 1181 patients admitted to the largest hospital in Qatar with COVID-19 pneumonia. The area under the curve (AUC), calibration curves, and other metrics were bootstrapped to examine the performance of the models. Variables constituting the CURB-65 and PSI scores underwent further analysis using the Least Absolute Shrinkage and Selection Operator (LASSO) along with logistic regression to develop a model predicting CCI. Complex machine learning models were built for comparative analysis. RESULTS: The PSI performed better than CURB-65 in predicting 30-day mortality (AUC 0.83, 0.78 respectively), while CURB-65 outperformed PSI in predicting CCI (AUC 0.78, 0.70 respectively). The modified PSI/CURB-65 model (respiratory rate, oxygen saturation, hematocrit, age, sodium, and glucose) predicting CCI had excellent accuracy (AUC 0.823) and good calibration. CONCLUSIONS: Our study recalibrated, externally validated the PSI and CURB-65 for predicting 30-day mortality and CCI, and developed a model for predicting CCI. Our tool can potentially guide clinicians in Qatar to stratify patients with COVID-19 pneumonia.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Cuidados Críticos , Mortalidade Hospitalar , Humanos , Pneumonia/diagnóstico , Pneumonia/terapia , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença
12.
Trials ; 22(1): 571, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454594

RESUMO

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of hospitalization worldwide. Bed rest with low levels of physical activity is common during periods of hospitalization and leads to functional decline as well as increased risk of complications. The aim of this study is to assess the effect of supervised physical training during hospitalization with CAP compared with standard usual care for CAP on length of hospital stay, risk of readmission, mortality risk, physical capacity, muscle and fat mass, muscle strength, metabolic function, systemic inflammation, health-related quality of life, and physical activity level. METHODS: This study is a randomized controlled trial with three parallel experimental arms. Based on a sample size calculation, a total of 210 patients admitted with CAP at Nordsjællands Hospital, Hillerød, Denmark, will be recruited. Patients will be randomly allocated (1:1:1) to either (1) standard usual care, (2) standard usual care combined with in-bed cycling, or (3) standard usual care combined with exercises from a booklet. The primary outcome is differences in length of hospital stay between groups, with secondary outcomes being differences between groups in time to (1) 90-day readmission and (2) 180-day mortality. Further secondary outcomes are differences in changes from baseline between groups in (3) lean mass, (4) fat mass, (5) fat-free mass, (6) physical capacity, (7) health-related quality of life, (8) systemic inflammation, and (9) physical activity level after discharge. Data on length of hospital stay, readmission, and mortality will be collected from patient files, while total lean, fat, and fat-free mass will be quantitated by dual-energy x-ray absorptiometry and bioelectrical impedance analysis. Physical function will be assessed using grip strength, 30-s chair stand tests, and Barthel Index-100. Health-related quality of life will be assessed with the EQ-5D-5L questionnaire. Systemic inflammation will be assessed in blood samples, while accelerometers are used for measuring physical activity. DISCUSSION: If a simple physical training program appears to diminish the impact of critical illness and hospitalization on clinical outcome, mobility, and health-related quality of life, it may lead to novel therapeutic approaches in the treatment of patients hospitalized with CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094636 . Registered on 1 April 2019.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/terapia , Exercício Físico , Humanos , Tempo de Internação , Pneumonia/diagnóstico , Pneumonia/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Arch. argent. pediatr ; 119(4): e345-e348, agosto 2021. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1281782

RESUMO

El talco, un silicato de magnesio hidratado, formó parte durante décadas del cuidado tradicional de lactantes y niños pequeños. Si bien en los niños su inhalación aguda, que suele ser accidental durante el cambio de pañales, no es frecuente, es una condición potencialmente peligrosa, que puede provocar dificultad respiratoria grave e incluso cuadros mortales. Se describe el grave compromiso respiratorio por neumonitis química asociado con la inhalación accidental de talco en un lactante de 14 meses. El niño presentó un cuadro de dificultad respiratoria con requerimiento de asistencia respiratoria mecánica (ARM) durante una semana. En cuanto al tratamiento, no existe un estándar, se utilizaron antibióticos y corticoides sistémicos y aerosolterapia. No presentó complicaciones en otros órganos o sistemas. Su evolución fue favorable, se pudo externar al décimo día de internación y presentó posteriormente episodios aislados de hiperreactividad bronquial.


Talc is a hydrated magnesium silicate. It was part of traditional infant and young child care for decades. In children, its acute inhalation, generally accidental during diaper changes, although not frequent, is a potentially dangerous condition, and can cause severe respiratory distress and even death. We describe the case of a 14-month child who had an accidental inhalation of talc, chemical pneumonitis and severe respiratory compromise. The patient had acute respiratory distress syndrome requiring mechanical ventilation for one week. There is no standard treatment, we used systemic antibiotics and corticosteroids and aerosol therapy. He did not have complications in other organs or systems. He was hospitalized for ten days. In the follow up, he had isolated episodes of bronchial hyperresponsiveness.


Assuntos
Humanos , Masculino , Lactente , Pneumonia/induzido quimicamente , Insuficiência Respiratória/induzido quimicamente , Talco/efeitos adversos , Pneumonia/terapia , Respiração Artificial , Insuficiência Respiratória/terapia , Acidentes Domésticos , Inalação , Intubação Intratraqueal
14.
Arch. argent. pediatr ; 119(4): S171-S197, agosto 2021. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1281039

RESUMO

Las infecciones respiratorias agudas bajas (IRAB) continúan representando una importante causa de morbimortalidad en nuestro medio. El manejo normatizado de casos constituye una valiosa herramienta para enfrentarlas.Además de los aspectos relacionados con el diagnóstico y tratamiento de estas enfermedades, el análisis de factores de riesgo (tanto biológicos como socioambientales), desde una perspectiva local y actual, permitie implementar medidas efectivas de control y/o prevención, así como identificar aquellos pacientes susceptibles de presentar formas graves o complicaciones.Desde 1996 la Sociedad Argentina de Pediatría asumió el desafío de generar un documento que guíe el manejo integral de los pacientes con IRAB. En esta cuarta actualización se incluyen los últimos adelantos en el tema.


Acute lower respiratory infections (ARI) continue being an important cause of morbidity and mortality in our region. Standardized case management is a valuable tool to deal with them.In addition to aspects related to the diagnosis and treatment of these diseases, the analysis of risk factors (both biological and socio-environmental) from a local and current perspective, allows the implementation of effective control and/or prevention measures, as well as identifying those patients susceptible to presenting serious forms or complications.Since 1996, the Sociedad Argentina de Pediatría asumed the challenge of generating a document that guides the comprehensive management of patients with ARI. This fourth update includes the latest advances on the subject.


Assuntos
Humanos , Recém-Nascido , Lactente , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/terapia , Pneumonia/diagnóstico , Pneumonia/terapia , Pneumonia/epidemiologia , Infecções Respiratórias/epidemiologia , Bronquiolite/diagnóstico , Bronquiolite/terapia , Bronquiolite/epidemiologia , Doença Aguda , Fatores de Risco
15.
Clin Immunol ; 229: 108801, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34280577

RESUMO

Major histocompatibility class I deficiency, due to genetic lesions in TAP1, TAP2, TAPBP, or B2M, manifests with recurrent sinopulmonary infections and granulomatous skin ulceration, and is predominately treated with antimicrobial prophylaxis and chest physiotherapy. One previous report of hematopoietic stem cell transplantation has been described in the literature, demonstrating cure of the immune defect without significant graft-versus-host disease. In this report, we expand the literature on HSCT in MHC-I deficiency with follow-up of the original patient, demonstrating maintained resolution of normal immune function and regression of the granulomatous rash 15 years post-transplant, and describe a further patient with mycobacterial disease whose transplant course was complicated by severe graft-versus-host disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Classe I/genética , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/terapia , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Criança , Deleção Cromossômica , Evolução Fatal , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mutação com Perda de Função , Pneumonia/imunologia , Pneumonia/terapia , Doenças da Imunodeficiência Primária/imunologia , Complexo de Endopeptidases do Proteassoma/deficiência , Complexo de Endopeptidases do Proteassoma/genética , Linfócitos T/imunologia , Adulto Jovem
16.
BMC Health Serv Res ; 21(1): 667, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34229679

RESUMO

BACKGROUND: With an estimated 24,000 deaths per year, pneumonia is the single largest cause of death among young children in Bangladesh, accounting for 18% of all under-5 deaths. The Government of Bangladesh adopted the WHO recommended Integrated Management of Childhood Illness (IMCI)-strategy in 1998 for outpatient management of pneumonia, which was scaled-up nationally by 2014. This paper reports the service availability and readiness related to IMCI-based pneumonia management in Bangladesh. We conducted a secondary analysis of the Bangladesh Health Facility Survey-2017, which was conducted with a nationally representative sample including all administrative divisions and types of health facilities. We limited our analysis to District Hospitals (DHs), Maternal and Child Welfare Centres (MCWCs), Upazila (sub-district) Health Complexes (UHCs), and Union Health and Family Welfare Centres (UH&FWCs), which are mandated to provide IMCI services. Readiness was reported based on 10 items identified by national experts as 'essential' for pneumonia management. RESULTS: More than 90% of DHs and UHCs, and three-fourths of UH&FWCs and MCWCs provide IMCI-based pneumonia management services. Less than two-third of the staff had ever received IMCI-based pneumonia training. Only one-third of the facilities had a functional ARI timer or a watch able to record seconds on the day of the visit. Pulse oximetry was available in 27% of the district hospitals, 18% of the UHCs and none of the UH&FWCs. Although more than 80% of the facilities had amoxicillin syrup or dispersible tablets, only 16% had injectable gentamicin. IMCI service registers were not available in nearly one-third of the facilities and monthly reporting forms were not available in around 10% of the facilities. Only 18% of facilities had a high-readiness (score 8-10), whereas 20% had a low-readiness (score 0-4). The readiness was significantly poorer among rural and lower level facilities (p < 0.001). Seventy-two percent of the UHCs had availability of one of any of the four oxygen sources (oxygen concentrators, filled oxygen cylinder with flowmeter, filled oxygen cylinder without flowmeter, and oxygen distribution system) followed by DHs (66%) and MCWCs (59%). CONCLUSION: There are substantial gaps in the readiness related to IMCI-based pneumonia management in public health facilities in Bangladesh. Since pneumonia remains a major cause of child death nationally, Bangladesh should make a substantial effort in programme planning, implementation and monitoring to address these critical gaps to ensure better provision of essential care for children suffering from pneumonia.


Assuntos
Serviços de Saúde da Criança , Pneumonia , Bangladesh/epidemiologia , Criança , Pré-Escolar , Instalações de Saúde , Humanos , Pneumonia/epidemiologia , Pneumonia/terapia , População Rural
17.
Life Sci ; 282: 119792, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229006

RESUMO

AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.


Assuntos
Angiotensina I/metabolismo , Asma/terapia , Fragmentos de Peptídeos/metabolismo , Pneumonia/terapia , Angiotensina I/sangue , Animais , Asma/sangue , Asma/metabolismo , Modelos Animais de Doenças , Terapia por Exercício , Masculino , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/sangue , Pneumonia/sangue , Pneumonia/metabolismo
18.
Ann Am Thorac Soc ; 18(7): 1087-1097, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34242148

RESUMO

Pneumonia causes a significant burden of disease worldwide. Although all populations are at risk of pneumonia, those at extremes of age and those with immunosuppressive disorders, underlying respiratory disease, and critical illness are particularly vulnerable. Although clinical practice guidelines addressing the management and treatment of pneumonia exist, few of the supporting studies focus on the crucial contributions of the host in pneumonia pathogenesis and recovery. Such essential considerations include the host risk factors that lead to susceptibility to lung infections; biomarkers reflecting the host response and the means to pursue host-directed pneumonia therapy; systemic effects of pneumonia on the host; and long-term health outcomes after pneumonia. To address these gaps, the Pneumonia Working Group of the Assembly on Pulmonary Infection and Tuberculosis led a workshop held at the American Thoracic Society meeting in May 2018 with overarching objectives to foster attention, stimulate research, and promote funding for short-term and long-term investigations into the host contributions to pneumonia. The workshop involved participants from various disciplines with expertise in lung infection, pneumonia, sepsis, immunocompromised patients, translational biology, data science, genomics, systems biology, and clinical trials. This workshop report summarizes the presentations and discussions and important recommendations for future clinical pneumonia studies. These recommendations include establishing consensus disease and outcome definitions, improved phenotyping, development of clinical study networks, standardized data and biospecimen collection and protocols, and development of innovative trial designs.


Assuntos
Pneumonia , Consenso , Estado Terminal , Humanos , Hospedeiro Imunocomprometido , Pneumonia/terapia , Relatório de Pesquisa , Estados Unidos
19.
Clin Sci (Lond) ; 135(14): 1733-1750, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34236078

RESUMO

Chronic obstructive pulmonary disease (COPD) is a worldwide chronic inflammatory lung disease, and influenza A virus (IAV) infection is a common cause of acute exacerbations of COPD (AECOPD). Therefore, targeting viral infections represents a promising strategy to prevent the occurrence and development of inflammatory flare ups in AECOPD. Jianpiyifei II (JPYFII) is a traditional herbal medicine used in China to treat patients with COPD, and its clinical indications are not well understood. However, investigation of the anti-inflammatory effects and underlying mechanism using an animal model of smoking have been reported in a previous study by our group. In addition, some included herbs, such as Radix astragali and Radix aupleuri, were reported to exhibit antiviral effects. Therefore, the aim of the present study was to investigate whether JPYFII formulation relieved acute inflammation by clearing the IAV in a mouse model that was exposed to cigarette smoke experimentally. JPYFII formulation treatment during smoke exposure and IAV infection significantly reduced the number of cells observed in bronchoalveolar lavage fluid (BALF), expression of proinflammatory cytokines, chemokines, superoxide production, and viral load in IAV-infected and smoke-exposed mice. However, JPYFII formulation treatment during smoke exposure alone did not reduce the number of cells in BALF or the expression of Il-6, Tnf-a, and Il-1ß. The results demonstrated that JPYFII formulation exerted an antiviral effect and reduced the exacerbation of lung inflammation in cigarette smoke (CS)-exposed mice infected with IAV. Our results suggested that JPYFII formulation could potentially be used to treat patients with AECOPD associated with IAV infection.


Assuntos
Medicina Herbária , Vírus da Influenza A/patogenicidade , Pneumonia/terapia , Doença Pulmonar Obstrutiva Crônica/terapia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Influenza Humana/complicações , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumaça/efeitos adversos , Fumar/efeitos adversos
20.
Front Immunol ; 12: 663986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122422

RESUMO

Immunotherapy that includes programmed cell death-1 (PD-1), programmed cell death- ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors has revolutionized the therapeutic strategy in multiple malignancies. Although it has achieved significant breakthrough in advanced non-small cell lung cancer patients, immune-related adverse events (irAEs) including checkpoint inhibitor pneumonitis (CIP), are widely reported. As the particularly worrisome and potentially lethal form of irAEs, CIP should be attached more importance. Especially in non-small cell lung cancer (NSCLC) patients, the features of CIP may be more complicated on account of the overlapping respiratory signs compromised by primary tumor following immunotherapy. Herein, we included the previous relevant reports and comprehensively summarized the characteristics, diagnosis, and management of CIP. We also discussed the future direction of optimal steroid therapeutic schedule for patients with CIP in NSCLC based on the current evidence.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/complicações , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/complicações , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/etiologia , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteínas de Checkpoint Imunológico/genética , Proteínas de Checkpoint Imunológico/metabolismo , Incidência , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/etiologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Prognóstico , Índice de Gravidade de Doença , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo
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