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2.
BMJ Open ; 12(9): e051307, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109034

RESUMO

OBJECTIVES: This study was designed to evaluate the effect of rehabilitation in preventing decreased functional status (FS) after community-acquired pneumonia (CAP) in elderly patients. DESIGN: This was a retrospective observational study. SETTING: Multicentre study was conducted in two medical facilities from January 2016 to December 2018. PARTICIPANTS: Hospitalised patients with CAP aged over 64 years were enrolled. FS was assessed by the Barthel Index (BI) (range, 0-100, in 5-point increments) at admission and before discharge and graded into three categories: independent, BI 80-100; semidependent, BI 30-75; and dependent, BI 0-25. Multivariable analysis of factors contributing to decreased FS was conducted with two groups: with a decrease of at least one category (decreased group) or without a decrease of category (maintained group). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the effect of rehabilitation in preventing decreased FS. The secondary outcomes were factors associated with decreased FS. RESULTS: The maintained and decreased groups included 400 and 138 patients, respectively. A high frequency of rehabilitation therapy was observed in the decreased group (189 (47.3%) vs 104 (75.4%); p<0.001). Multivariable analysis showed that the factors affecting FS were aspiration pneumonia, Pneumonia Severity Index (PSI) category V, length of stay and age (OR 2.66, 95% CI 1.58 to 4.49; OR 1.92, 95% CI 1.29 to 3.44; OR 1.05, 95% CI 1.04 to 1.07; and OR 1.05, 95% CI 1.02 to 1.09, respectively). After adjusting for factors contributing to decreased FS, rehabilitation showed a limited effect in preventing decreased FS in 166 matched pairs by McNemar's test (p=0.327). CONCLUSIONS: Aspiration and PSI played important roles in reducing FS. The effect of rehabilitation remains unclear in CAP. TRIAL REGISTRATION NUMBER: UMIN000046362.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Idoso , Infecções Comunitárias Adquiridas/terapia , Estado Funcional , Humanos , Pneumonia/terapia , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Lancet Glob Health ; 10(10): e1494-e1504, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36113533

RESUMO

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.


Assuntos
Infecções Pneumocócicas , Pneumonia , Portador Sadio/epidemiologia , Criança , Estudos de Coortes , Humanos , Lactente , Nepal/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae
4.
BMC Endocr Disord ; 22(1): 233, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115983

RESUMO

BACKGROUND: In subjects with hypothyroidism, edema is often observed, and pleural effusion and pericardial fluid could be also observed. The color of such fluid retention is usually yellow. Here we show a very rare case with hypothyroidism who had bloody pleural effusion and bloody pericardial fluid. CASE PRESENTATION: A 42-year-old male noticed chest pain and the aggravation of exertional dyspnea, and he was transported to our institution by emergency. He had Graves' disease and underwent total thyroidectomy about 4 years before. After then, he had been treated with 200 µg/day of levothyroxine sodium for the maintenance of thyroid function. However, he self-interrupted such medication about 2 years before. Thyroid function on admission was reduced as follows: free triiodothyronine, 1.60 pg/mL; free thyroxine < 0.40 ng/dL; thyroid-stimulating hormone 25.50 µU/mL. Inflammation markers were increased: white blood cells 25,280 /µL; C-reactive protein 18.66 mg/dL. A large amount of pericardial fluid and pleural effusion were observed in chest and abdominal computer tomography and echocardiography. In addition, we performed pleural effusion and pericardial fluid collection. Pleural effusion in this subject showed bloody color, but not yellow. In cell block specimen of pleural effusion and pericardial fluid, red blood cells, neutrophils and lymphocyte component were observed. In this subject, however, we were unable to find any obvious background disease causing bloody pericardial effusion. Finally, we concluded that bloody pleural effusion and bloody pericardial fluid were brought about in a subject with untreated known hypothyroidism after total thyroidectomy, triggered by pneumonia. CONCLUSIONS: In subjects with hypothyroidism, fluid and mucopolysaccharide are stored in interstitial space and protein osmolality is increased, thus leading to edema and fluid retention. It is noted here that pleural effusion and pericardial fluid in this subject showed bloody color and included red blood cells. There are no reports of bloody pericardial fluid with hypothyroidism. Therefore, it is important to keep in mind that a subject with some trigger, such as infection, may have a hematologic fluid retention that is not seen when hypothyroidism is present alone, as observed in this subject.


Assuntos
Doença de Graves , Hipotireoidismo , Derrame Pericárdico , Derrame Pleural , Pneumonia , Adulto , Proteína C-Reativa , Glicosaminoglicanos , Doença de Graves/complicações , Humanos , Hipotireoidismo/complicações , Masculino , Derrame Pericárdico/complicações , Derrame Pleural/etiologia , Pneumonia/complicações , Tireoidectomia/efeitos adversos , Tireotropina , Tiroxina , Tri-Iodotironina
5.
Cochrane Database Syst Rev ; 9: CD006338, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066373

RESUMO

BACKGROUND: Despite conflicting evidence, chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia. This is an update of a review first published in 2010 and updated in 2013. OBJECTIVES: To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults. SEARCH METHODS: We updated our searches in the following databases to May 2022: the Cochrane Central Register of Controlled Trials (CENTRAL) via OvidSP, MEDLINE via OvidSP (from 1966), Embase via embase.com (from 1974), Physiotherapy Evidence Database (PEDro) (from 1929), CINAHL via EBSCO (from 2009), and the Chinese Biomedical Literature Database (CBM) (from 1978). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of chest physiotherapy for treating pneumonia in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included two new trials in this update (540 participants), for a total of eight RCTs (974 participants). Four RCTs were conducted in the United States, two in Sweden, one in China, and one in the United Kingdom. The studies looked at five types of chest physiotherapy: conventional chest physiotherapy; osteopathic manipulative treatment (OMT, which includes paraspinal inhibition, rib raising, and myofascial release); active cycle of breathing techniques (which includes active breathing control, thoracic expansion exercises, and forced expiration techniques); positive expiratory pressure; and high-frequency chest wall oscillation. We assessed four trials as at unclear risk of bias and four trials as at high risk of bias. Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving mortality, but the certainty of evidence is very low (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.15 to 7.13; 2 trials, 225 participants; I² = 0%). OMT (versus placebo) may have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.43, 95% CI 0.12 to 1.50; 3 trials, 327 participants; I² = 0%). Similarly, high-frequency chest wall oscillation (versus no physiotherapy) may also have little to no effect on improving mortality, but the certainty of evidence is very low (RR 0.75, 95% CI 0.17 to 3.29; 1 trial, 286 participants). Conventional chest physiotherapy (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.93, 95% CI 0.56 to 1.55; 2 trials, 225 participants; I² = 85%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on improving cure rate, but the certainty of evidence is very low (RR 0.60, 95% CI 0.29 to 1.23; 1 trial, 32 participants). OMT (versus placebo) may improve cure rate, but the certainty of evidence is very low (RR 1.59, 95% CI 1.01 to 2.51; 2 trials, 79 participants; I² = 0%). OMT (versus placebo) may have little to no effect on mean duration of hospital stay, but the certainty of evidence is very low (mean difference (MD) -1.08 days, 95% CI -2.39 to 0.23; 3 trials, 333 participants; I² = 50%). Conventional chest physiotherapy (versus no physiotherapy, MD 0.7 days, 95% CI -1.39 to 2.79; 1 trial, 54 participants) and active cycle of breathing techniques (versus no physiotherapy, MD 1.4 days, 95% CI -0.69 to 3.49; 1 trial, 32 participants) may also have little to no effect on duration of hospital stay, but the certainty of evidence is very low. Positive expiratory pressure (versus no physiotherapy) may reduce the mean duration of hospital stay by 1.4 days, but the certainty of evidence is very low (MD -1.4 days, 95% CI -2.77 to -0.03; 1 trial, 98 participants). Positive expiratory pressure (versus no physiotherapy) may reduce the duration of fever by 0.7 days, but the certainty of evidence is very low (MD -0.7 days, 95% CI -1.36 to -0.04; 1 trial, 98 participants). Conventional chest physiotherapy (versus no physiotherapy, MD 0.4 days, 95% CI -1.01 to 1.81; 1 trial, 54 participants) and OMT (versus placebo, MD 0.6 days, 95% CI -1.60 to 2.80; 1 trial, 21 participants) may have little to no effect on duration of fever, but the certainty of evidence is very low. OMT (versus placebo) may have little to no effect on the mean duration of total antibiotic therapy, but the certainty of evidence is very low (MD -1.07 days, 95% CI -2.37 to 0.23; 3 trials, 333 participants; I² = 61%). Active cycle of breathing techniques (versus no physiotherapy) may have little to no effect on duration of total antibiotic therapy, but the certainty of evidence is very low (MD 0.2 days, 95% CI -4.39 to 4.69; 1 trial, 32 participants). High-frequency chest wall oscillation plus fibrobronchoscope alveolar lavage (versus fibrobronchoscope alveolar lavage alone) may reduce the MD of intensive care unit (ICU) stay by 3.8 days (MD -3.8 days, 95% CI -5.00 to -2.60; 1 trial, 286 participants) and the MD of mechanical ventilation by three days (MD -3 days, 95% CI -3.68 to -2.32; 1 trial, 286 participants), but the certainty of evidence is very low. One trial reported transient muscle tenderness emerging after OMT in two participants. In another trial, three serious adverse events led to early withdrawal after OMT. One trial reported no adverse events after positive expiratory pressure treatment. Limitations of this review were the small sample size and unclear or high risk of bias of the included trials. AUTHORS' CONCLUSIONS: The inclusion of two new trials in this update did not change the main conclusions of the original review. The current evidence is very uncertain about the effect of chest physiotherapy on improving mortality and cure rate in adults with pneumonia. Some physiotherapies may slightly shorten hospital stays, fever duration, and ICU stays, as well as mechanical ventilation. However, all of these findings are based on very low certainty evidence and need to be further validated.


Assuntos
Modalidades de Fisioterapia , Pneumonia , Terapia Respiratória , Adulto , Antibacterianos/uso terapêutico , Humanos , Modalidades de Fisioterapia/efeitos adversos , Pneumonia/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , Terapia Respiratória/efeitos adversos
6.
J Exp Med ; 219(11)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36112363

RESUMO

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Interferon Tipo I , Pneumonia , Vacina contra Febre Amarela , Autoanticorpos , Humanos
7.
BMC Anesthesiol ; 22(1): 296, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114451

RESUMO

BACKGROUND: This study was designed to examine extubation time and to determine its association with postoperative pneumonia (POP) after meningioma resection. METHODS: We studied extubation time for 598 patients undergoing meningioma resection from January 2016 to December 2020. Extubation time was analysed as a categorical variable and patients were grouped into extubation within 21 minutes, 21-35 minutes and ≥ 35 minutes. Our primary outcome represented the incidence of POP. The association between extubation time and POP was assessed using multivariable logistic regression mixed-effects models which adjusted for confounders previously reported. Propensity score matching (PSM) was also performed at a ratio of 1:1 to minimize potential bias. RESULTS: Among 598 patients (mean age 56.1 ± 10.7 years, 75.8% female), the mean extubation time was 32.4 minutes. Extubation was performed within 21 minutes (32.4%), 21-35 minutes (31.2%) and ≥ 35 minutes (36.4%), respectively, after surgery. Older patients (mean age 57.8 years) were prone to delayed extubation (≥ 35 min) in the operating room, and more inclined to perioperative fluid infusion. When extubation time was analysed as a continuous variable, there was a U-shaped relation of extubation time with POP (P for nonlinearity = 0.044). After adjustment for confounders, extubation ≥35 minutes was associated with POP (odds ratio [OR], 2.73 95% confidence interval [CI], 1.36 ~ 5.47). Additionally, the results after PSM were consistent with those before matching. CONCLUSIONS: Delayed extubation after meningioma resection is associated with increased pneumonia incidence. Therefore, extubation should be performed as early as safely possible in the operation room.


Assuntos
Neoplasias Meníngeas , Meningioma , Pneumonia , Idoso , Extubação/efeitos adversos , Feminino , Humanos , Masculino , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
8.
Front Cell Infect Microbiol ; 12: 929856, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046746

RESUMO

Objective: To evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) and culture in pathogen detection among intensive care unit (ICU) and non-ICU patients with suspected pulmonary infection. Methods: In this prospective study, sputum samples were collected from patients with suspected pulmonary infection for 2 consecutive days and then subjected to DNA or RNA sequencing by mNGS or culture; 62 ICU patients and 60 non-ICU patients were admitted. In the end, comparisons were made on the pathogen species identified by mNGS and culture, the overall performance of these two methods in pathogen detection, and the most common pathogens detected by mNGS between the ICU and non-ICU groups. Results: In DNA and RNA sequencing, the positive rate of pathogen detection reached 96.69% (117/121) and 96.43% (108/112), respectively. In culture tests, the positive rate of the pathogen was 39.34% (48/122), much lower than that of DNA and RNA sequencing. In general, the positive rate of pathogen detection by sputum mNGS was significantly higher than that of sputum culture in the total and non-ICU groups (p < 0.001) but did not show a significant difference when compared to the result of sputum culture in the ICU group (p = 0.08). Haemophilus spp., Candida albicans, Enterococcus spp., and viruses from the mNGS results were excluded before comparing the overall performance of these two methods in pathogen detection. Specifically, among the 10 most common bacteria implied from the mNGS results, significant differences were observed in the number of cases of Haemophilus parainfluenzae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Enterococcus faecalis between the ICU and non-ICU groups (p < 0.05). Conclusions: This study demonstrated the superiority of mNGS over culture in detecting all kinds of pathogen species in sputum samples. These results indicate that mNGS may serve as a valuable tool to identify pathogens, especially for ICU patients who are more susceptible to mixed infections.


Assuntos
Metagenômica , Pneumonia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenoma , Metagenômica/métodos , Pneumonia/microbiologia , Estudos Prospectivos , Sensibilidade e Especificidade
9.
BMJ Open Respir Res ; 9(1)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36104104

RESUMO

BACKGROUND: The ROX index (Respiratory rate-OXygenation) has been described as a prediction tool to identify the need for invasive mechanical ventilation (IMV) in community-acquired pneumonia (CAP) with acute hypoxaemic respiratory failure treated with high-flow nasal cannula in order to avoid delay of a necessary intubation. However, its use in predicting the need for ventilatory support in hospitalised patients with CAP has not been validated. METHODS: This is a retrospective cohort study including subjects with CAP treated in the general ward, emergency service or intensive care unit of a third-level centre in Cundinamarca, Colombia, between January 2001 and February 2020. The ROX index was estimated as the ratio of oxygen saturation/fraction of inspired oxygen to respiratory rate. RESULTS: A total of 895 patients were included, of whom 93 (10%) required IMV. The ROX index proved to be a good predictor, presenting an area under the curve of receiver operating characteristics (AUROC) of 0.733 (95% CI 0.671 to 0.795, p<0.001) when determined by pulse oximetry and an AUROC of 0.779 (95% CI 0.699 to 0.859, p<0.001) when estimated by arterial blood gas (ABG) parameters, with an intraclass correlation of 0.894. The estimated cut-off point was 14.8; a score less than 14.8 indicates high risk of requiring IMV. CONCLUSION: The ROX index is a good predictor of IMV in hospitalised patients with CAP. It presents good performance when calculated through pulse oximetry and can replace the one calculated by ABG.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Insuficiência Respiratória , Infecções Comunitárias Adquiridas/terapia , Humanos , Pneumonia/terapia , Respiração Artificial , Insuficiência Respiratória/terapia , Estudos Retrospectivos
10.
Drug Des Devel Ther ; 16: 3023-3039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105322

RESUMO

Abstract: Inflammation and oxidative stress play a major role in the development of sepsis and its associated complications, leading to multiple organ failure and death. The lungs, liver, and kidneys are among the early affected organs correlated with mortality in sepsis. Alpha-chymotrypsin (α-ch) is a serine protease that exerts anti-inflammatory, anti-edematous, and anti-oxidant properties. Purpose: This study was undertaken to elucidate if the anti-inflammatory and anti-oxidant effects of α-ch observed in previous studies can alleviate lung, liver, and kidney injuries in a cecal ligation and puncture (CLP)-induced sepsis model, and thus decrease mortality. Materials and Methods: Septic animals were given α-ch 2 h post CLP procedure. Sepsis outcomes were assessed in the lungs, liver, and kidneys. Separate animal groups were investigated for a survival study. Results: CLP resulted in 0% survival, while α-chymotrypsin post-treatment led to 50% survival at the end of the study. Administration of α-chymotrypsin resulted in a significant attenuation of sepsis-induced elevated malonaldehyde (MDA) and total nitrite/nitrate (NOx) levels. In addition, there was a significant increase in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity in the lungs, liver, and kidneys. Administration of α-ch reduced elevated tissue expression of toll-like receptor-4 (TLR4), nuclear factor kappa-B (NF-κB), myeloperoxidase (MPO), and inducible nitric oxide synthase (iNOS). Alpha-chymotrypsin resulted in a significant reduction in serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6). Alpha-chymotrypsin attenuated the rise in serum creatinine, cystatin C, blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels that was observed in the septic group. In addition, α-ch significantly reduced the lung wet/dry weight ratio, total protein content, and leukocytic counts in bronchoalveolar lavage fluid (BALF). Histopathological examination of the lungs, liver, and kidneys confirmed the protective effects of α-ch on those organs. Conclusion: α-ch has protective potential against sepsis through lowering tissue expression of TLR4, NF-κB, MPO, and iNOS leading to decreased oxidative stress and inflammatory signals induced by sepsis. This effect appeared to alleviate the damage to the lungs, liver, and kidneys and increase survival in rats subjected to sepsis.


Assuntos
Pneumonia , Sepse , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Quimotripsina , Inflamação/metabolismo , Rim , Fígado/metabolismo , Pulmão , NF-kappa B/metabolismo , Pneumonia/metabolismo , Punções , Ratos , Sepse/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo
11.
Can Respir J ; 2022: 9149385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106062

RESUMO

Introduction: This study is conducted to investigate the correlation between perioperative fractional exhaled nitric oxide and postoperative pneumonia (POP) and the feasibility of perioperative FeNO for predicting POP in surgical lung cancer patients. Methods: Patients who were diagnosed with non-small-cell lung cancer (NSCLC) were prospectively analyzed, and the relationship between perioperative FeNO and POP was evaluated based on patients' basic characteristics and clinical data in the hospital. Results: There were 218 patients enrolled in this study. Finally, 183 patients were involved in the study, with 19 of them in the POP group and 164 in the non-POP group. The POP group had significantly higher postoperative FeNO (median: 30.0 vs. 19.0 ppb, P < 0.001) as well as change in FeNO (median: 10.0 vs. 0.0 ppb, P < 0.001) before and after the surgery. For predicting POP based on the receiver operating characteristic (ROC) curve, a cutoff value of 25 ppb for postoperative FeNO (Youden's index: 0.515, sensitivity: 78.9%, and specificity: 72.6%) and 4 ppb for change in FeNO (Youden's index: 0.610, sensitivity: 84.2%, specificity: 76.8%) were selected. Furthermore, according to the bivariate regression analysis, FEV1/FVC (OR = 0.948, 95% CI: 0.899-0.999, P=0.048), POD1 FeNO (OR = 1.048, 95% CI: 1.019-1.077, P=0.001), and change in FeNO (OR = 1.087, 95% CI: 1.044-1.132, P < 0.001) were significantly associated with occurrence of POP. Conclusions: This prospective study revealed that a high postoperative FeNO (>25 ppb), as well as an increased change in FeNO (>4 ppb), may have the potential in detecting the occurrence of POP in surgical lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Testes Respiratórios , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Óxido Nítrico/análise , Pneumonia/diagnóstico , Estudos Prospectivos
13.
Pak J Biol Sci ; 25(7): 602-607, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36098166

RESUMO

<b>Background and Objective:</b> <i>Kalanchoe tomentosa</i> is identified and their different characteristics regarding the antibacterial and antioxidant properties have a vast effect. Fresh <i>K. tomentosa</i> leaves obtained from Bandung, Indonesia was extracted using n-hexane followed by serial dichloromethane maceration. <b>Materials and Methods:</b> N-hexane and ethyl acetate were used to separate the dichloromethane extract using vacuum liquid chromatography and the isolated compounds were recrystallized with n-hexane. <b>Results:</b> About 37 mg of dichloromethane extract was obtained from the extraction process. Recrystallized compound isolates were identified as stigmast-5-en-3-ol or ß-sitosterol. Both dichloromethane extract and ß-sitosterol isolated compounds showed strong bacteriostatic activity against <i>S. aureus</i> with MIC = 15.63 and 7.81 µg mL<sup></sup><sup>1</sup> and<i> K. pneumonia</i> with MIC = 7.81 and 31.25 µg mL<sup></sup><sup>1</sup>, respectively. However, only dichloromethane extract exhibited a bactericidal effect (7.81 µg mL<sup></sup><sup>1</sup>). <b>Conclusion:</b> The pure ß-sitosterol compound was isolated from<i> K. tomentosa</i> dichloromethane extract. Both the dichloromethane extract and the isolated ß-sitosterol compound had antibacterial effects against <i>S. aureus</i> and <i>K. pneumonia.</i>.


Assuntos
Kalanchoe , Pneumonia , Antibacterianos/química , Antibacterianos/farmacologia , Klebsiella , Cloreto de Metileno , Extratos Vegetais/química , Folhas de Planta/química , Sitosteroides , Staphylococcus aureus
14.
Int J Chron Obstruct Pulmon Dis ; 17: 2149-2160, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101790

RESUMO

Purpose: The objective of this study was to assess the clinical and cost benefits of treating patients with chronic obstructive pulmonary disease (COPD) according to global and national guidelines compared to real-life clinical practice in the United States and three European countries (Belgium, Germany, Sweden). Patients and Methods: A cost-consequence model was developed to compare current prescribing patterns with two alternative scenarios, the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022) recommendations and the second with national guidelines. Costs and clinical outcomes were modeled for these alternative scenarios over a time horizon of one year, based on real-world evidence and health insurance data. Results: Current clinical practice in each of the countries was inconsistent with published recommendations. A redistribution to prescribing patterns according to global and national recommendations led to a substantial decrease in the use of inhaled corticosteroid (ICS) containing therapies of more than 80% and 44%, respectively. There was a reduced incidence of up to 16% of mild-to-moderate pneumonia and up to 29% of severe pneumonia. Exacerbations decreased across all countries apart from Sweden, where a small increase in the rate of exacerbations was due to the redistribution of some patients currently undergoing inhaled triple therapy to non-ICS-containing therapies. Adapting treatment to recommendations could provide potential cost savings of up to 13% in estimated annual direct costs, resulting predominantly from the reduction in cost of healthcare resource use, including hospitalization associated with treating incident pneumonia, particularly severe pneumonia. Cost savings for prevalent adult patients with COPD on long-acting inhaler therapy ranged from €31 to €675 per patient per year. Conclusion: Redistribution of COPD patients from current clinical practice to treatment according to published recommendations would provide clinical benefits and substantial cost savings.


Assuntos
Pneumonia , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Adulto , Bélgica/epidemiologia , Broncodilatadores/uso terapêutico , Humanos , Pneumonia/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Suécia/epidemiologia , Estados Unidos
15.
Int J Chron Obstruct Pulmon Dis ; 17: 2161-2174, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101793

RESUMO

Purpose: To determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting ß2-agonist (LABA), and long-acting muscarinic antagonist (LAMA). Patients and Methods: This was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted. Results: Of 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57-0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001). Conclusion: ICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.


Assuntos
Pneumonia , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Idoso , Broncodilatadores , Feminino , Humanos , Masculino , Antagonistas Muscarínicos , Pneumonia/induzido quimicamente , Pneumonia/complicações , Pneumonia/diagnóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos , Espanha
16.
Front Immunol ; 13: 918507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045672

RESUMO

Chronic pulmonary inflammation and chronic obstructive pulmonary disease (COPD) are major health issues largely due to air pollution and cigarette smoke (CS) exposure. The role of the innate receptor NLRP3 (nucleotide-binding domain and leucine-rich repeat containing protein 3) orchestrating inflammation through formation of an inflammasome complex in CS-induced inflammation or COPD remains controversial. Using acute and subchronic CS exposure models, we found that Nlrp3-deficient mice or wild-type mice treated with the NLRP3 inhibitor MCC950 presented an important reduction of inflammatory cells recruited into the bronchoalveolar space and of pulmonary inflammation with decreased chemokines and cytokines production, in particular IL-1ß demonstrating the key role of NLRP3. Furthermore, mice deficient for Caspase-1/Caspase-11 presented also decreased inflammation parameters, suggesting a role for the NLRP3 inflammasome. Importantly we showed that acute CS-exposure promotes NLRP3-dependent cleavage of gasdermin D in macrophages present in the bronchoalveolar space and in bronchial airway epithelial cells. Finally, Gsdmd-deficiency reduced acute CS-induced lung and bronchoalveolar space inflammation and IL-1ß secretion. Thus, we demonstrated in our model that NLRP3 and gasdermin D are key players in CS-induced pulmonary inflammation and IL-1ß release potentially through gasdermin D forming-pore and/or pyroptoctic cell death.


Assuntos
Fumar Cigarros , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Animais , Caspase 1/metabolismo , Fumar Cigarros/efeitos adversos , Células Epiteliais/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Tabaco/metabolismo
17.
Respir Res ; 23(1): 239, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088316

RESUMO

INTRODUCTION: Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The "network of excellence on Community Acquired Pneumonia" (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research. METHODS: To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat. RESULTS: Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications. CONCLUSION: Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients' risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/terapia , Europa (Continente)/epidemiologia , Humanos , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/terapia , SARS-CoV-2
18.
Arthritis Res Ther ; 24(1): 210, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050717

RESUMO

BACKGROUND: Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc). METHODS: The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation. Microarray-based gene expression analysis and serum protein profiling were performed in the BLM-induced SSc models. The effect of MT-7117 on transforming growth factor-ß (TGF-ß)-induced activation of human dermal fibroblasts was evaluated in vitro. Immunohistochemical analyses of MC1R expression in the skin of SSc patients were performed. RESULTS: Prophylactic treatment with MT-7117 (≥ 0.3 mg/kg/day p.o.) significantly inhibited skin fibrosis and lung inflammation, and therapeutic treatment with MT-7117 (≥ 3 mg/kg/day p.o.) significantly suppressed the development of skin fibrosis in the BLM-induced SSc models. Gene array analysis demonstrated that MT-7117 exerts an anti-inflammatory effect via suppression of the activation of inflammatory cells and inflammation-related signals; additionally, vascular dysfunction was extracted as the pathology targeted by MT-7117. Serum protein profiling revealed that multiple SSc-related biomarkers including P-selectin, osteoprotegerin, cystatin C, growth and differentiation factor-15, and S100A9 were suppressed by MT-7117. MT-7117 inhibited the activation of human dermal fibroblasts by suppressing TGF-ß-induced ACTA2 (encoding α-smooth muscle actin) mRNA elevation. MC1R was expressed by monocytes/macrophages, neutrophils, blood vessels (endothelial cells), fibroblasts, and epidermis (keratinocytes) in the skin of SSc patients, suggesting that these MC1R-positive cells could be targets for MT-7117. CONCLUSIONS: MT-7117 demonstrates disease-modifying effects in preclinical models of SSc. Investigations of its mechanism of action and target expression analyses indicate that MT-7117 exerts its positive effect by affecting inflammation, vascular dysfunction, and fibrosis, which are all key pathologies of SSc. The results of the present study suggest that MT-7117 is a potential therapeutic agent for SSc. A phase 2 clinical trial investigating the efficacy and tolerability of MT-7117 in patients with early, progressive diffuse cutaneous SSc is currently in progress.


Assuntos
Pneumonia , Escleroderma Sistêmico , Animais , Bleomicina/toxicidade , Proteínas Sanguíneas , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Fibrose , Humanos , Inflamação/patologia , Camundongos , Pneumonia/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/metabolismo , Transdução de Sinais/fisiologia , Pele/patologia , Fator de Crescimento Transformador beta/metabolismo
19.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077293

RESUMO

Pneumonia is an acute infectious disease with high morbidity and mortality rates. Pneumonia's development, severity and outcome depend on age, comorbidities and the host immune response. In this study, we combined theoretical and experimental investigations to characterize pneumonia and its comorbidities as well as to assess the host immune response measured by TREC/KREC levels in patients with pneumonia. The theoretical study was carried out using the Columbia Open Health Data (COHD) resource, which provides access to clinical concept prevalence and co-occurrence from electronic health records. The experimental study included TREC/KREC assays in young adults (18-40 years) with community-acquired (CAP) (n = 164) or nosocomial (NP) (n = 99) pneumonia and healthy controls (n = 170). Co-occurring rates between pneumonia, sepsis, acute respiratory distress syndrome (ARDS) and some other related conditions common in intensive care units were the top among 4170, 3382 and 963 comorbidities in pneumonia, sepsis and ARDS, respectively. CAP patients had higher TREC levels, while NP patients had lower TREC/KREC levels compared to controls. Low TREC and KREC levels were predictive for the development of NP, ARDS, sepsis and lethal outcome (AUCTREC in the range 0.71-0.82, AUCKREC in the range 0.67-0.74). TREC/KREC analysis can be considered as a potential prognostic test in patients with pneumonia.


Assuntos
Pneumonia , Síndrome do Desconforto Respiratório , Sepse , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Pneumonia/epidemiologia , Síndrome do Desconforto Respiratório/epidemiologia , Sepse/complicações , Sepse/epidemiologia , Adulto Jovem
20.
J Antimicrob Chemother ; 77(Supplement_1): i77-i83, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065725

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review AMR in Kuwait and initiatives underway addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Kuwait and to improve patient outcomes. METHODS: National initiatives to address AMR, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from a clinician in Kuwait were sought to contextualize this information. CONCLUSIONS: In Kuwait there have been some initiatives addressing AMR such as annual campaigns for proper use of antibiotics. Antibiotic use is high but there appears to be a low understanding in the general public about their appropriate use. However, there is legislation in place prohibiting over-the-counter purchase of antibiotics. Only international guidelines for CA-RTIs are used. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Kuwait, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical patient outcomes.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Infecções Respiratórias , Doença Aguda , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Acesso aos Serviços de Saúde , Humanos , Kuweit/epidemiologia , Pneumonia/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia
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