RESUMO
Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.
Assuntos
Lesão Pulmonar Aguda , Bleomicina , Indóis , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fenilcarbamatos , Pneumonia , Sulfonamidas , Receptor 4 Toll-Like , Compostos de Tosil , Animais , Bleomicina/efeitos adversos , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêutico , Camundongos , Indóis/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfonamidas/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/patologia , Pneumonia/induzido quimicamente , Pneumonia/prevenção & controle , Pneumonia/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Modelos Animais de Doenças , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacosRESUMO
BACKGROUND: Postoperative pneumonia is a common but serious complication in patients with lung cancer. This meta-analysis aims to evaluate the effect of respiratory exercise on reducing postoperative pneumonia in patients with lung cancer and to provide a reliable basis for clinical treatment and nursing of patients with lung cancer. METHODS: Two reviewers searched PubMed, Embase, Web of Science, Cochrane Library, China Knowledge Network, Wanfang, and Weipu databases. We searched for the randomized controlled trials (RCTs) published in Chinese or English on the breathing exercises in patients with lung cancer up to January 30, 2024. The quality of the literature was evaluated with the Cochrane Risk of Bias Tool 2 (ROB 2). RevMan 5.3 software was used for meta-analysis. RESULTS: Eleven RCTs with 1429 patients with lung cancer were included, and 710 patients received breathing exercises. The meta-analysis results showed that breathing exercises could significantly reduce the incidence of postoperative pneumonia [RR = 0.35, 95%CI (0.25, 0.51)], improve the FEV1 [MD = - 0.49, 95%CI (- 0.73, - 0.24)], FVC [MD = - 0.59, 95%CI (- 0.83, - 0.35)] in patients with lung cancer (all P < 0.05). There were significant differences in the incidence of pneumonia for patients undergoing breathing exercises with single exercise time ≥ 15 min (RR = 0.37, 95%CI 0.24 ~ 0.62), breathing exercises for 1 week (RR = 0.29, 95%CI 0.16 ~ 0.55) or for 2 weeks (RR = 0.48, 95%CI 0.28 ~ 0.85) and breathing exercises > 4 times (RR = 0.36, 95%CI 0.23 ~ 0.57) per day (all P < 0.05). CONCLUSION: Breathing exercises have shown the capacity to augment pulmonary function in patients with lung cancer, concurrently mitigating the risk of postoperative pneumonia.
Assuntos
Exercícios Respiratórios , Neoplasias Pulmonares , Pneumonia , Complicações Pós-Operatórias , Humanos , Exercícios Respiratórios/métodos , Neoplasias Pulmonares/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Pneumonia/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Pneumonia is the largest cause of mortality in Canadian lambs. Currently there are no licensed ovine vaccines in Canada to reduce economic losses from this production-limiting disease. Objective animals and procedure: The effectiveness of an experimental subunit Mannheimia haemolytica leukotoxin A (LtxA) and transferrin binding protein B (TbpB) vaccine was evaluated in lambs for reduction of clinical disease in an experimental challenge study and in a controlled randomized field trial in a large commercial sheep operation. Results: Following an experimental challenge of parainfluenza 3 virus and M. haemolytica, the subunit vaccine induced significantly higher LtxA and TbpB antibody titers at 48 d post-challenge compared to the adjuvant and Ovipast Plus bacterin (Merck Animal Health), but there were no significant differences in clinical signs or mortality among vaccine groups. Following vaccination of commercial ewes and their lambs at weaning, the only significant difference in health, growth, and carcass traits between vaccinates and non-vaccinates was a slightly higher pneumonia treatment rate in vaccinated preweaned lambs (25.7%) compared to unvaccinated preweaned lambs (23.4%) (P = 0.04). Conclusion and clinical relevance: Although vaccination with the experimental subunit M. haemolytica vaccine induced high LtxA and TbpB antibodies, it did not reduce clinical disease in lambs following an experimental challenge study or in a controlled randomized field trial in a commercial sheep operation. Further research is required to identify additional protective antigens for a safe and effective ovine respiratory vaccine to reduce pneumonia losses in commercial sheep flocks.
Efficacité d'un vaccin respiratoire sous-unitaire expérimental de Mannheimia haemolytica ovin à réduire la pneumonie chez les agneaux. Contexte: La pneumonie est la principale cause de mortalité chez les agneaux canadiens. Présentement, il n'y a aucun vaccin ovin homologué au Canada pour réduire les pertes économiques associées à cette pathologie limitant la production. Objectif animaux et procédure: L'efficacité d'un vaccin sous-unitaire expérimental à base de la leucotoxine A (LtxA) et de la protéine B liant la transferrine (TbpB) de Mannheimia haemolytica a été évalué chez des agneaux pour la réduction de la maladie clinique lors d'une infection expérimentale et lors d'un essai de champs randomisé et contrôlé dans un grand élevage commercial de moutons. Résultats: À la suite d'une infection expérimentale avec le virus parainfluenza 3 et M. haemolytica, le vaccin sous-unitaire a induit des titres d'anticorps significativement plus élevés contre LtxA et TbpB à 48 j post-infection comparativement à l'adjuvant et à la bactérine Ovipast Plus (Merck Santé Animale), mais il n'y avait aucune différence significative dans les signes cliniques ou la mortalité parmi les groupes vaccinés. À la suite de la vaccination de brebis commerciales et de leurs agneaux au moment du sevrage, la seule différence significative dans la santé, la croissance et les caractéristiques des carcasses entre les animaux vaccinés et non-vaccinés était un taux légèrement plus élevé de traitement de la pneumonie chez les agneaux vaccinés pré-sevrage (25,7 %) comparativement aux agneaux non-vaccinés au présevrage (23,4 %) (P = 0,04). Conclusion et pertinence clinique: Bien que la vaccination avec le vaccin sous-unitaire expérimental M. haemolytica ait induit des taux d'anticorps élevés contre LtxA et TbpB, il n'a pas réduit la maladie clinique chez les agneaux à la suite d'une infection expérimentale ou lors d'un essai clinique randomisé contrôlé dans un élevage ovin commercial. Des recherches supplémentaires sont requises pour identifier des antigènes protecteurs additionnels pour un vaccin respiratoire ovin efficace pour réduire les pertes associées à la pneumonie dans les troupeaux ovins commerciaux.(Traduit par Dr Serge Messier).
Assuntos
Vacinas Bacterianas , Mannheimia haemolytica , Doenças dos Ovinos , Vacinas de Subunidades Antigênicas , Animais , Mannheimia haemolytica/imunologia , Ovinos , Doenças dos Ovinos/prevenção & controle , Vacinas Bacterianas/imunologia , Feminino , Vacinas de Subunidades Antigênicas/imunologia , Pneumonia/veterinária , Pneumonia/prevenção & controle , Masculino , Anticorpos Antibacterianos/sangue , Pasteurelose Pneumônica/prevenção & controle , Pasteurelose Pneumônica/imunologiaRESUMO
Pseudomonas aeruginosa is a complex nosocomial infectious agent responsible for numerous illnesses, with its growing resistance variations complicating treatment development. Studies have emphasized the importance of virulence factors OprE and OprF in pathogenesis, highlighting their potential as vaccine candidates. In this study, B-cell, MHC-I, and MHC-II epitopes were identified, and molecular linkers were active to join these epitopes with an appropriate adjuvant to construct a vaccine. Computational tools were employed to forecast the tertiary framework, characteristics, and also to confirm the vaccine's composition. The potency was weighed through population coverage analysis and immune simulation. This project aims to create a multi-epitope vaccine to reduce P. aeruginosa-related illness and mortality using immunoinformatics resources. The ultimate complex has been determined to be stable, soluble, antigenic, and non-allergenic upon inspection of its physicochemical and immunological properties. Additionally, the protein exhibited acidic and hydrophilic characteristics. The Ramachandran plot, ProSA-web, ERRAT, and Verify3D were employed to ensure the final model's authenticity once the protein's three-dimensional structure had been established and refined. The vaccine model showed a significant binding score and stability when interacting with MHC receptors. Population coverage analysis indicated a global coverage rate of 83.40%, with the USA having the highest coverage rate, exceeding 90%. Moreover, the vaccine sequence underwent codon optimization before being cloned into the Escherichia coli plasmid vector pET-28a (+) at the EcoRI and EcoRV restriction sites. Our research has developed a vaccine against P. aeruginosa that has strong binding affinity and worldwide coverage, offering an acceptable way to mitigate nosocomial infections.
Assuntos
Biologia Computacional , Infecções por Pseudomonas , Pseudomonas aeruginosa , Sepse , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/genética , Humanos , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Sepse/prevenção & controle , Sepse/imunologia , Sepse/microbiologia , Biologia Computacional/métodos , Epitopos/imunologia , Epitopos/química , Pneumonia/prevenção & controle , Pneumonia/imunologia , Pneumonia/microbiologia , Vacinas contra Pseudomonas/imunologia , Vacinas Bacterianas/imunologia , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/genéticaRESUMO
BACKGROUND: A randomized trial suggested that treatment with metoclopramide reduces the risk of pneumonia in patients with acute stroke and a nasogastric tube. We assessed whether this finding could be replicated in a post hoc analysis of the randomized PRECIOUS trial (Prevention of Complications to Improve Outcome in Elderly Patients With Acute Stroke). METHODS: PRECIOUS was an international, 3×2 partial-factorial, randomized controlled, open-label clinical trial with blinded outcome assessment assessing preventive treatment with metoclopramide, paracetamol, and ceftriaxone in patients aged ≥66 years with acute ischemic stroke or intracerebral hemorrhage and a National Institutes of Health Stroke Scale score ≥6. In the present study, we analyzed patients who had a nasogastric tube within 24 hours after randomization. Patients who were allocated to metoclopramide (10 mg TID) were compared with patients who were not. Treatment was started within 24 hours after symptom onset and continued for 4 days or until discharge if earlier. The primary outcome was pneumonia in the first week after stroke. The score on the modified Rankin Scale after 90 days was a secondary outcome and analyzed with ordinal logistic regression. RESULTS: From April 2016 through June 2022, a total of 1493 patients were enrolled with 1376 included in this analysis, of whom 1185 (86%) had ischemic stroke and 191 (14%) had intracerebral hemorrhage. The first day after randomization, 329 (23.9%) patients had a nasogastric tube, of whom 156 were allocated to metoclopramide and 173 to standard care. Metoclopramide was not associated with a reduction of pneumonia (41.0% versus 35.8%; adjusted odds ratio, 1.35 [95% CI, 0.79-2.30]) or with poor functional outcome (adjusted odds ratio, 1.07 [95% CI, 0.71-1.61]). CONCLUSIONS: In patients with stroke who had a nasogastric tube shortly after stroke onset, metoclopramide for 4 days did not reduce pneumonia or have an effect on the functional outcome.
Assuntos
Intubação Gastrointestinal , Metoclopramida , Pneumonia , Humanos , Metoclopramida/uso terapêutico , Idoso , Masculino , Feminino , Pneumonia/prevenção & controle , Pneumonia/etiologia , Pneumonia/tratamento farmacológico , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Ceftriaxona/uso terapêutico , Acetaminofen/uso terapêutico , AVC Isquêmico/prevenção & controle , AVC Isquêmico/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Resultado do TratamentoRESUMO
Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.
Assuntos
Queimaduras , Endotoxemia , Inflamação , Mucosa Intestinal , Estresse Oxidativo , Animais , Queimaduras/metabolismo , Queimaduras/complicações , Queimaduras/mortalidade , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Endotoxemia/mortalidade , Endotoxemia/tratamento farmacológico , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos dos fármacos , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Masculino , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Superóxido Dismutase/metabolismo , Lipopolissacarídeos/farmacologia , Pneumonia/prevenção & controle , Camundongos Endogâmicos C57BL , Vitaminas/uso terapêutico , Vitaminas/farmacologia , Modelos Animais de DoençasRESUMO
Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Peptídeos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Humanos , Animais , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , Camundongos , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/uso terapêutico , Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Antivirais/química , Linhagem Celular , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia/prevenção & controle , Pulmão/virologia , Pulmão/patologia , FemininoRESUMO
BACKGROUND AND OBJECTIVES: Dysphagia is a common complication following stroke. It corresponds to the development of pneumonia, which is always associated with bad prognosis, longer hospital stays and increased mortality. The aim of the study was to assess the impact of physical therapy intervention of dysphagia on preventing pneumonia in acute stroke patients. METHODS: A single-blind randomized controlled trial was carried out on 70 ischemic stroke patients with oropharyngeal dysphagia, age ranged from 49 to 65 years. They were randomly assigned to two groups (control and study) of equal number. Patients in the control group received oral care and nasogastric tube feeding, while patients in the study group received the same program in addition to the designed physical therapy program (exercises and neuromuscular electrical stimulation). The intervention program was applied for 40 min/session, 1 session/day, and 5 days/week for 4 weeks. Gugging swallowing screen (GUSS), and stroke associated pneumonia (SAP) control and prevention criteria were used to assess dysphagia and incidence of pneumonia at baseline, after two and 4 weeks of intervention for both groups. RESULTS: Before treatment, all patients were susceptible to pneumonia after two and 4 weeks of intervention; there were a significant increase in GUSS score in both groups with more improvement in favor of the study group (p < 0.05) and a statistically significant increase in incidence of SAP after 2 weeks of intervention only in the control group (p < 0.05). The results also showed a significant negative correlation between GUSS score and SAP (r = - 0.3662, p = 0.0018) IMPLICATIONS FOR PHYSIOTHERAPY PRACTICE: adding physical therapy (exercise therapy and neuromuscular electrical stimulation) to oral care and nasogastric tube feeding is effective in improving oropharyngeal dysphagia and decreasing the incidence of aspiration pneumonia in acute ischemic stroke patients.
Assuntos
Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/reabilitação , Transtornos de Deglutição/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Método Simples-Cego , Idoso , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Pneumonia/prevenção & controle , Pneumonia/complicações , Modalidades de FisioterapiaRESUMO
Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. KEY POINTS: â¢A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. â¢The whole genome was determined, analyzed, and compared to other phages. â¢Assaying the effect of phage in preventing infection in neutrophil-deficient models.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Genoma Viral , Acinetobacter baumannii/virologia , Acinetobacter baumannii/genética , Animais , Infecções por Acinetobacter/prevenção & controle , Infecções por Acinetobacter/microbiologia , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/fisiologia , Ratos , Terapia por Fagos/métodos , Composição de Bases , Modelos Animais de Doenças , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão/virologia , Pulmão/microbiologia , Pneumonia/prevenção & controle , Pneumonia/microbiologia , Pneumonia/virologia , MasculinoRESUMO
We aimed to analyze the effects of exclusive breastfeeding duration on the occurrence and course of pneumonia in infants aged up to 6 months. Prospective case-control study. This study was conducted from August 2020 to August 2022 at a maternity and child health hospital in China. A total of 218 infants up to 6 months of age with pneumonia were included in the analyses. Health data were obtained using a hospitalization information system or an interview-based questionnaire. Univariate and multivariate logistic regression analyses were performed to analyze the data. The incidence of pneumonia, hospitalization duration, and costs to participants were significantly affected by the duration of exclusive breastfeeding (p < 0.01). The incidence of pneumonia among participants with different exclusive breastfeeding durations also differed significantly (p < 0.01). The shorter the duration of exclusive breastfeeding, the higher the incidence of pneumonia among infants. We found that the longer the exclusive breastfeeding duration in infants up to 6 months of age, the lower the recurrence of pneumonia, the shorter the hospital stay, and the lower the hospital costs. The rate of exclusive breastfeeding for infants up to 6 months of age should be increased as much as possible to reduce the occurrence of pneumonia and hospital costs.
Assuntos
Aleitamento Materno , Pneumonia , Humanos , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Lactente , Feminino , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Masculino , Estudos Prospectivos , China/epidemiologia , Recém-Nascido , Incidência , Fatores de Tempo , Inquéritos e Questionários , Hospitalização/estatística & dados numéricosAssuntos
Procedimentos Cirúrgicos Eletivos , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Pneumonia , Complicações Pós-Operatórias , Humanos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Masculino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Pneumonia/prevenção & controle , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
There is insufficient evidence that angiotensin-converting enzyme inhibitors (ACEIs) can reduce pneumonia by inducing a dry cough that confers a protective effect on the airway. To increase the evidence base on the clinical use of ACEIs for pneumonia prevention, this retrospective cohort study aimed to comparatively examine the risk of pneumonia-related hospitalization between ACEI initiators and angiotensin II receptor blocker (ARB) initiators using claims data from two Japanese municipalities. We identified persons who were newly prescribed any ACEI or ARB as their first antihypertensive agent between April 2016 and March 2020. The Fine-Gray method was applied to a Cox proportional hazards model to estimate the subdistribution hazard ratio (HR) of ACEI use (reference: ARB use) for pneumonia-related hospitalization, with death treated as a competing risk. Sex, age, comorbidities, medications, and pneumococcal immunization were included as covariates. The analysis was conducted on 1421 ACEI initiators and 9040 ARB initiators, and the adjusted subdistribution HR of ACEI use was estimated to be 1.21 (95% confidence interval: 0.89-1.65; P = 0.22). ACEI initiation did not demonstrate any significant preventive effect against pneumonia-related hospitalization relative to ARB initiation. There remains a lack of strong evidence on the protective effects of ACEIs, and further research is needed to ascertain the benefits of their use in preventing pneumonia. We conducted a large-scale retrospective cohort study using real-world healthcare data from a Japanese population. In this study, ACEI initiation did not indicate a significant preventive effect against pneumonia-related hospitalization.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Hospitalização , Pneumonia , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Masculino , Estudos Retrospectivos , Feminino , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Adulto , Japão/epidemiologia , Hipertensão/tratamento farmacológico , Idoso de 80 Anos ou mais , Estudos de Coortes , Anti-Hipertensivos/uso terapêuticoRESUMO
BACKGROUND: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. METHODS: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. RESULTS: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. CONCLUSIONS: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. SYSTEMATIC REVIEW PROTOCOL: INPLASY 202410068.
Assuntos
Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/epidemiologia , Respiração com Pressão Positiva/métodos , Pneumopatias/etiologia , Pneumopatias/epidemiologia , Pneumopatias/prevenção & controle , Respiração Artificial/métodos , Atelectasia Pulmonar/prevenção & controle , Atelectasia Pulmonar/etiologia , Atelectasia Pulmonar/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/prevenção & controleRESUMO
BACKGROUND/AIM: We evaluated the usefulness of prophylactic mini-tracheostomy (PMT) and perioperative administration of tazobactam/piperacillin (TAZ/PIPC) in high-risk patients after esophagectomy. PATIENTS AND METHODS: We retrospectively studied 89 consecutive high-risk patients who underwent esophagectomy for esophageal cancer between January 2013 and December 2021. We defined patients with two or more of the following factors as high risk: age ≥70 years, performance status ≥1, respiratory dysfunction, liver dysfunction, cardiac dysfunction, renal dysfunction, diabetes mellitus, albumin <3.5 g/dl, and Brinkman index >600. Standard management was administered to the first 50 patients (standard group). PMT and TAZ/PIPC were administered to the next 39 patients (combination group). Patient characteristics and short-term outcomes were compared before and after propensity-score matching. RESULTS: Before propensity-score matching, 24-hour urine creatinine clearance, retrosternal route, 3-field lymph node dissection, and open abdominal approach were more common, postoperative pneumonia (13% vs. 36%, p=0.045) and complications of grade ≥3b (2.6% vs. 22%, p=0.01) were less frequent, and the postoperative hospital stay was shorter (median: 23 vs. 28 days, p=0.022) in the combination group than in the standard group. In propensity-score matching, patient characteristics, except for 24-h creatinine clearance and reconstructive route, were matched for 23 paired patients. Postoperative pneumonia (8.7% vs. 39%, p=0.035) and complications of grade ≥3b (0% vs. 26%, p=0.022) were less frequent and postoperative hospital stay was shorter (median: 22 vs. 25 days, p=0.021) in the combination group than in the standard group. CONCLUSION: PMT with TAZ/PIPC can potentially prevent postoperative pneumonia in high-risk patients after esophagectomy.
Assuntos
Neoplasias Esofágicas , Esofagectomia , Combinação Piperacilina e Tazobactam , Pneumonia , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Idoso , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Neoplasias Esofágicas/cirurgia , Pneumonia/prevenção & controle , Pneumonia/etiologia , Pneumonia/epidemiologia , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/administração & dosagem , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Estudos Retrospectivos , Fatores de RiscoRESUMO
Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.
Assuntos
Nanotubos de Carbono , Triterpenos Pentacíclicos , Pneumonia , Transdução de Sinais , Triterpenos , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanotubos de Carbono/toxicidade , NF-kappa B/metabolismo , Triterpenos Pentacíclicos/farmacologia , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Pneumonia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologiaRESUMO
Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies.
Assuntos
Antígenos , Tolerância Imunológica , Nanopartículas , Ovalbumina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células Th2 , Animais , Células Th2/imunologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Ovalbumina/imunologia , Ovalbumina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tolerância Imunológica/efeitos dos fármacos , Antígenos/administração & dosagem , Antígenos/imunologia , Camundongos , Pneumonia/imunologia , Pneumonia/prevenção & controle , Feminino , Camundongos Endogâmicos BALB C , Hipersensibilidade/imunologia , Citocinas/imunologia , Modelos Animais de DoençasRESUMO
OBJECTIVES: To summarize current evidence of high-dose influenza vaccine (HD-IV) vs standard-dose (SD-IV) regarding severe clinical outcomes. METHODS: A prespecified meta-analysis was conducted to assess relative vaccine effectiveness (rVE) of HD-IV vs SD-IV in reducing the rates of (1) pneumonia and influenza (P&I) hospitalization, (2) all hospitalizations, and (3) all-cause death in adults ≥ 65 years in randomized controlled trials. Pooled effect sizes were estimated using fixed-effects models with the inverse variance method. RESULTS: Five randomized trials were included encompassing 105,685 individuals. HD-IV vs SD-IV reduced P&I hospitalizations (rVE: 23.5 %, [95 %CI: 12.3 to 33.2]). HD-IV vs SD-IV also reduced rate of all-cause hospitalizations (rVE: 7.3 %, [95 %CI: 4.5 to 10.0]). No significant differences were observed in death rates (rVE = 1.6 % ([95 %CI: -2.0 to 5.0]) in HD-IV vs SD-IV. Sensitivity analyses omitting trials with participants sharing the same comorbidity, trials with ≥ 100 events, and random-effects models provided comparable estimates for all outcomes. CONCLUSIONS: HD-IV reduced the incidence of P&I and all-cause hospitalization vs SD-IV in adults ≥ 65 years in randomized trials, through no significant difference was observed in all-cause death rates. These findings, supported by evidence from several randomized studies, can benefit from replication in a fully powered, individually randomized trial.
Assuntos
Hospitalização , Vacinas contra Influenza , Influenza Humana , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Hospitalização/estatística & dados numéricos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/mortalidade , Idoso , Eficácia de Vacinas , Pneumonia/prevenção & controle , Pneumonia/mortalidade , Masculino , Idoso de 80 Anos ou mais , FemininoRESUMO
Cigarette smoke is one of the main factors in Chronic Obstructive Pulmonary Disease (COPD), a respiratory syndrome marked by persistent respiratory symptoms and increasing airway obstruction. Perturbed NAD+/NADH levels may play a role in various diseases, including lung disorders like COPD. In our study, we investigated the preventive effect of NADH supplementation in an experimental model of COPD induced by cigarette smoke extract (CSE). N = 64 mice randomly distributed in eight groups were injected with NADH (two doses of 100 mg/kg or 200 mg/kg) or dexamethasone (2 mg/kg) before being exposed to CSE for up to 9 weeks. Additionally, NADH supplementation preserved lung antioxidant defenses by preventing the functional loss of key enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase, and the expression levels of glutathione (GSH) (n = 4, p < 0.001). It also reduced oxidative damage markers, such as malondialdehyde (MDA) and nitrites (n = 4, p < 0.001). A marked increase in tissue myeloperoxidase activity was assessed (MPO), confirming neutrophils implication in the inflammatory process. The latter was significantly ameliorated in the NADH-treated groups (p < 0.001). Finally, NADH prevented the CSE-induced secretion of cytokines such as Tumor Necrosis Factor alpha (TNF-α), IL-17, and IFN-y (n = 4, p < 0.001). Our study shows, for the first time, the clinical potential of NADH supplementation in preventing key features of COPD via its unique anti-inflammatory and antioxidant properties.
Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , NAD , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Animais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/etiologia , NAD/metabolismo , Camundongos , Pneumonia/prevenção & controle , Pneumonia/metabolismo , Pneumonia/patologia , Injeções Intraperitoneais , Fumaça/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Citocinas/metabolismo , Pulmão/patologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Peroxidase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.