RESUMO
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.
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COVID-19/virologia , SARS-CoV-2/fisiologia , SARS-CoV-2/patogenicidade , Replicação Viral , Animais , Anticorpos Neutralizantes , COVID-19/diagnóstico por imagem , COVID-19/patologia , Cricetinae , Humanos , Imunogenicidade da Vacina , Pulmão/patologia , Mesocricetus , Camundongos , Glicoproteína da Espícula de Coronavírus/genética , Microtomografia por Raio-XRESUMO
Next generation sequencing (NGS)-based tumor profiling identified an overwhelming number of uncharacterized somatic mutations, also known as variants of unknown significance (VUS). The therapeutic significance of EGFR mutations outside mutational hotspots, consisting of >50 types, in nonsmall cell lung carcinoma (NSCLC) is largely unknown. In fact, our pan-nation screening of NSCLC without hotspot EGFR mutations (n = 3,779) revealed that the majority (>90%) of cases with rare EGFR mutations, accounting for 5.5% of the cohort subjects, did not receive EGFR-tyrosine kinase inhibitors (TKIs) as a first-line treatment. To tackle this problem, we applied a molecular dynamics simulation-based model to predict the sensitivity of rare EGFR mutants to EGFR-TKIs. The model successfully predicted the diverse in vitro and in vivo sensitivities of exon 20 insertion mutants, including a singleton, to osimertinib, a third-generation EGFR-TKI (R2 = 0.72, P = 0.0037). Additionally, our model showed a higher consistency with experimentally obtained sensitivity data than other prediction approaches, indicating its robustness in analyzing complex cancer mutations. Thus, the in silico prediction model will be a powerful tool in precision medicine for NSCLC patients carrying rare EGFR mutations in the clinical setting. Here, we propose an insight to overcome mutation diversity in lung cancer.
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Carcinoma Pulmonar de Células não Pequenas/genética , Genes erbB-1 , Neoplasias Pulmonares/genética , Acrilamidas/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Compostos de Anilina/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Simulação de Dinâmica Molecular , Mutação , Testes Farmacogenômicos , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidoresRESUMO
BACKGROUND: Accurate prognostic understanding in patients with advanced cancer is essential for shared decision making; however, patients may experience psychological burden through knowing the incurable nature of advanced cancer. It has been unclear how their prognostic understanding fluctuates and whether accurate prognostic understanding is associated with psychological distress from the time of diagnosis over time. MATERIALS AND METHODS: We longitudinally investigated prognostic understanding in 225 patients with newly diagnosed advanced lung cancer at 16 hospitals in Japan until 24 months after diagnosis. We examined associated factors with being consistently accurate in prognostic understanding, especially focusing on its association with psychological well-being. RESULTS: The proportion of patients with an inaccurate prognostic understanding remained approximately 20% over time with the presence of patients with inconsistent understanding. Patients with consistently accurate prognostic understanding showed a significantly lower Emotional Well-Being subscale score at both 3 and 6 months after diagnosis (p = .010 and p = .014, respectively). In multivariate analyses, being consistently accurate in prognostic understanding was significantly associated with female gender and higher lung cancer-specific symptom burden at 3 months (p = .008 and p = .005, respectively) and lower emotional well-being at 6 months (p = .006). CONCLUSION: Although substantial proportions of patients with advanced lung cancer had inaccurate prognostic understanding from the time of diagnosis over time, patients with consistently accurate prognostic understanding experienced greater psychological burden. Our findings highlight the importance of continuous psychological care and support for patients who understand their severe prognosis accurately. IMPLICATIONS FOR PRACTICE: This study demonstrated that approximately 20% of patients with advanced lung cancer had an inaccurate understanding about their prognosis, not only at the time of diagnosis but also at the later time points. Being consistently accurate in prognostic understanding was significantly associated with elevated levels of psychological distress. Although accurate prognostic understanding is essential for decision making for treatment and advance care planning, health care providers should be aware of psychological burdens in patients that accept their severe prognosis accurately. Appropriate care and support for such patients are warranted from diagnosis over time.
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Neoplasias Pulmonares , Angústia Psicológica , Feminino , Humanos , Japão , PrognósticoRESUMO
BACKGROUND: Both advanced cancer patients and their family caregivers experience distress and have a range of concerns after cancer diagnosis. However, longitudinal studies on this topic have been lacking. AIM: To investigate concerns in both patients with advanced lung cancer and their family caregivers longitudinally from diagnosis. DESIGN: A multi-center prospective questionnaire-based study. SETTING/PARTICIPANTS: We recruited patients with newly diagnosed advanced lung cancer and their family caregivers at 16 hospitals in Japan. We prospectively assessed the prevalence of their concerns using the Concerns Checklist and investigated the associations between their concerns and mental status as well as quality of life until 24 months after diagnosis. RESULTS: A total of 248 patients and their 232 family caregivers were enrolled. The prevalence of serious concerns was highest at diagnosis (patients: 68.3%, family caregivers: 65.3%). The most common serious concern was concern about the future in both groups at diagnosis (38.2% and 40.5%, respectively) and this remained high in prevalence over time, while the high prevalence of concern about lack of information improved 3 months after diagnosis in both groups. Approximately one-third of patient-family caregiver dyads had discrepant reports of serious concerns. The presence of serious concerns was significantly associated with anxiety and depression continuously in both groups. CONCLUSIONS: The majority of advanced lung cancer patients and their family caregivers have serious concerns from diagnosis, which is associated with their psychological distress. The spectrum of concerns alters over the disease trajectory, warranting efficient tailored care and support for both groups immediately after diagnosis.
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Cuidadores , Neoplasias Pulmonares , Humanos , Japão , Estudos Longitudinais , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: Fungal infections are rarely reported as a complication of bronchial thermoplasty (BT) in patients without immunosuppressive comorbidity. CASE PRESENTATION: A 19-year-old woman college student was admitted to our hospital owing to uncontrolled severe asthma despite using the maximum dose of steroid inhalation. She experienced asthmatic attacks more frequently while cheerleading, which is an extracurricular activity. She received BT because she wanted to continue cheerleading. After the second BT session, she developed more sputum and cough. During the third session, white secretion and saccular bronchodilation appeared in the left lower bronchus. Aspergillus fumigatus was detected in the culture of the bronchial lavage sample, and saccular bronchodilation in the affected bronchus was observed on computed tomography (CT). Five months after the start of oral itraconazole, her subjective symptoms as well as her CT findings improved. Her asthma condition improved enough for the patient to continue cheerleading without exacerbation. CONCLUSIONS: It is necessary to consider the possibility of respiratory tract infections including fungal infections after BT. Detailed observations of the entire bronchus and sample collection for microbial culture are highly recommended.
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Aspergilose Broncopulmonar Alérgica/etiologia , Asma/cirurgia , Termoplastia Brônquica/efeitos adversos , Antifúngicos/uso terapêutico , Aspergilose Broncopulmonar Alérgica/diagnóstico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Broncoscopia , Tosse/etiologia , Feminino , Humanos , Itraconazol/uso terapêutico , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Prognostic understanding in advanced cancer patients and their caregivers may have an impact on the delivery of effective care. The aims of this study were to explore prognostic understanding at diagnosis in both patients with advanced lung cancer and their caregivers and to investigate correlates of their understanding. SUBJECTS, MATERIALS, AND METHODS: A total of 193 patients with newly diagnosed advanced lung cancer and their 167 caregivers were enrolled at 16 hospitals in Japan. We assessed their perceptions of prognosis and goals of therapy and examined their associations with their sociodemographic characteristics, clinical status, quality of life, mood symptoms, and the status of disclosure of information by their treating physicians. RESULTS: One fifth of patients and caregivers (21.7% and 17.6%, respectively) mistakenly believed that the patients' cancer was "completely curable." Substantial proportions of them (16.9% and 10.3%, respectively) mistakenly believed that the primary goal of therapy was to remove all the cancer. Levels of anxiety and depression in both patients and caregivers were significantly higher among those who had accurate understanding of prognosis. In multivariate analyses, inaccurate perceptions of prognosis in patients were associated with sex, better emotional well-being, and lower lung cancer-specific symptom burden. Caregivers' inaccurate perceptions of patients' prognoses were associated with better performance status and better emotional well-being of patients. CONCLUSION: Substantial proportions of advanced lung cancer patients and their caregivers misunderstood their prognosis. Interventions to improve their accurate prognostic understanding should be developed with careful attention paid to its associated factors. IMPLICATIONS FOR PRACTICE: This study demonstrated that substantial proportions of patients with newly diagnosed advanced lung cancer and their caregivers had misunderstandings about their prognosis. Accurate perceptions of prognosis, which are indispensable in the delivery of effective care, were associated with elevated levels of anxiety and depression in both patients and caregivers, warranting psychosocial care and support for them immediately after diagnosis. Inaccurate perceptions of prognosis in patients were associated with better emotional well-being and lower lung cancer-specific symptom burden. Illness understanding in caregivers was associated with patients' physical and mental status. Those findings provide insight into how they obtain accurate illness understanding.
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Cuidadores/psicologia , Neoplasias Pulmonares/diagnóstico , Qualidade de Vida/psicologia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
Osimertinib is a highly active agent for patients with progression of lung cancer despite epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor treatment. This resistance is usually due to EGFR exon 20 T790M mutation, which can be detected by repeat biopsy. We report a case in which EGFR exon 20 T790M mutation was detected by repeat ascitic fluid examination. A 71-year-old woman with lung adenocarcinoma harboring EGFR exon 19 deletion was started on erlotinib(25 mg/day)as second-line therapy. Two years later, there was increase in pleural effusion, with concomitant malignant ascites; however, pathologic examination of the pleural and ascitic fluids did not detect EGFR T790Mmutation. Afatinib(2 0mg/day) was started, but there was no decrease in the severity of ascites. Two months later, her condition was extremely deteriorated. Finally, a much larger amount of ascitic fluid obtained by paracentesis was processed for cellblock, which demonstrated EGFR exon 20 T790M mutation. Thereafter, the ascites and the primary lesion dramatically decreased after treatment with osimerti- nib(80mg/day).
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Ascite/etiologia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Adenocarcinoma/complicações , Adenocarcinoma de Pulmão , Idoso , Éxons , Feminino , Humanos , Neoplasias Pulmonares/complicaçõesRESUMO
BACKGROUND: Some patients with severe asthma also have fungal sensitization and are considered to have severe asthma with fungal sensitization. However, there is limited information on the clinical features of SAFS. OBJECTIVE: To investigate the clinical characteristics of severe asthma with fungal sensitization. METHODS: The present study enrolled 124 patients with severe asthma. We evaluated clinical aspects, such as various serum cytokines, fractional exhaled nitric oxide, pulmonary function, and serum immunoglobulin E (IgE). Fungal sensitization was assessed by determining serum levels of IgE specific to fungal allergens (Aspergillus, Alternaria, Candida, Cladosporium, Penicillium, and Trichophyton species and Schizophyllum commune). The protocol was registered at a clinical trial registry (www.umin.ac.jp/ctr/index-j.htm; UMIN 000002980). RESULTS: Thirty-six patients (29%) showed sensitization to at least 1 fungal allergen. The most common species were Candida (16%), Aspergillus (11%), and Trichophyton (11%). The rate of early-onset asthma (<16 years of age) was higher in patients with fungal sensitization than in those without fungal sensitization (45% vs 25%; P = .02). Interleukin-33 levels were higher in patients with fungal sensitization than in those without fungal sensitization. Of patients with atopic asthma, Asthma Control Test scores were worse in patients with multiple fungal sensitizations than in patients with a single fungal sensitization or those without fungal sensitization. CONCLUSION: Severe asthma with fungal sensitization is characterized by early onset of disease and high serum levels of interleukin-33. Multiple fungal sensitizations are associated with poor asthma control. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR; www.umin.ac.jp/ctr/index-j.htm): UMIN 000002980.
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Alérgenos/imunologia , Antígenos de Fungos/imunologia , Asma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/sangue , Asma/metabolismo , Asma/fisiopatologia , Citocinas/sangue , Feminino , Volume Expiratório Forçado , Fungos/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Índice de Gravidade de Doença , Adulto JovemRESUMO
Influenza A viruses cause recurrent outbreaks at local or global scale with potentially severe consequences for human health and the global economy. Recently, a new strain of influenza A virus was detected that causes disease in and transmits among humans, probably owing to little or no pre-existing immunity to the new strain. On 11 June 2009 the World Health Organization declared that the infections caused by the new strain had reached pandemic proportion. Characterized as an influenza A virus of the H1N1 subtype, the genomic segments of the new strain were most closely related to swine viruses. Most human infections with swine-origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals do not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, we characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA04), as well as several other S-OIV isolates, in vitro and in vivo. In mice and ferrets, CA04 and other S-OIV isolates tested replicate more efficiently than a currently circulating human H1N1 virus. In addition, CA04 replicates efficiently in non-human primates, causes more severe pathological lesions in the lungs of infected mice, ferrets and non-human primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific-pathogen-free miniature pigs, CA04 replicates without clinical symptoms. The assessment of human sera from different age groups suggests that infection with human H1N1 viruses antigenically closely related to viruses circulating in 1918 confers neutralizing antibody activity to CA04. Finally, we show that CA04 is sensitive to approved and experimental antiviral drugs, suggesting that these compounds could function as a first line of defence against the recently declared S-OIV pandemic.
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Vírus da Influenza A Subtipo H1N1/fisiologia , Suínos/virologia , Animais , Anticorpos Antivirais/imunologia , Antivirais/farmacologia , Linhagem Celular , Cães , Feminino , Furões/virologia , Proteína HN/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Doenças dos Primatas/patologia , Doenças dos Primatas/virologia , Doenças dos Suínos/patologia , Doenças dos Suínos/virologia , Porco Miniatura/virologia , Replicação ViralRESUMO
BACKGROUND: Asthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of "TH2-high" asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma. METHODS: Serum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry. RESULTS: The serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics [70.0 (54.0-93.5) ng/ml] than in healthy subjects [57.0 (39.0-63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize "high-periostin" phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03-0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02-0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the "high-periostin" phenotype. CONCLUSION: Elevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.
Assuntos
Asma/sangue , Moléculas de Adesão Celular/sangue , Adulto , Povo Asiático , Aspirina , Asma/imunologia , Asma/fisiopatologia , Citocinas/sangue , Tolerância a Medicamentos , Eosinófilos/citologia , Feminino , Volume Expiratório Forçado , Humanos , Imunoglobulina E/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/sangue , Fenótipo , Rinite/sangue , Índice de Gravidade de Doença , Sinusite/sangue , Capacidade VitalRESUMO
BACKGROUND: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. METHODS: An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients' reports, physicians' records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. RESULTS: The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. CONCLUSIONS: Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized. TRIAL REGISTRATION: Clinical trial registered with UMIN (UMIN000003470).
Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Absorciometria de Fóton/métodos , Absorciometria de Fóton/normas , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico por imagem , Ansiedade/epidemiologia , Estudos de Coortes , Comorbidade , Depressão/diagnóstico por imagem , Depressão/epidemiologia , Feminino , Refluxo Gastroesofágico/diagnóstico por imagem , Refluxo Gastroesofágico/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID-19). METHODS: We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID-19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. RESULTS: The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C-reactive protein and elevated D-dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. INTERPRETATIONS: This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.
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COVID-19 , Humanos , COVID-19/epidemiologia , Feminino , Masculino , Fatores de Risco , Pessoa de Meia-Idade , Japão/epidemiologia , Idoso , Adulto , Síndrome de COVID-19 Pós-Aguda , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Transtornos da Memória/epidemiologia , Transtornos da Memória/etiologia , Idoso de 80 Anos ou mais , SARS-CoV-2 , População do Leste AsiáticoAssuntos
Bronquite/microbiologia , Influenza Humana/diagnóstico , Infecções Estafilocócicas/diagnóstico , Traqueíte/microbiologia , Idoso , Bronquite/diagnóstico , Bronquite/tratamento farmacológico , Bronquite/virologia , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Coinfecção/virologia , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/complicações , Masculino , Necrose/diagnóstico , Necrose/tratamento farmacológico , Necrose/microbiologia , Necrose/patologia , Infecções Estafilocócicas/complicações , Staphylococcus aureus/isolamento & purificação , Traqueíte/diagnóstico , Traqueíte/tratamento farmacológico , Traqueíte/virologia , Resultado do TratamentoRESUMO
OBJECTIVES: Some surgical cases of pleural empyema lead to death despite multidisciplinary treatment. The purpose of this study was to identify prognostic factors in cases treated surgically for pneumonia-associated pleural effusions and empyema caused by common bacteria. METHODS: We conducted a retrospective cohort study of 108 surgical patients of empyema who encountered at our hospital between 2011 and 2021. Patients were divided into surviving and non-surviving cases. Factors on admission (age, sex, body mass index, presence of fistula, performance status, pleural fluid culture results, HbA1c, albumin, leukocytes, hemoglobin, body temperature, heart rate, respiratory rate, systolic blood pressure, prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and RAPID score) were compared between the two groups. RESULTS: There were 87 cases of pleural empyema caused by pneumonia due to common bacteria. Variables that differed significantly in univariate analysis between the surviving and non-surviving cases in patients' characteristics on admission were fistula (p value < 0.001, odds ratio 20.000, 95% confidence interval 3.478-115.022), positive pleural fluid culture (0.016, 6.591, 1.190-36.502), body mass index < 18.5 (0.001, 16.857, 1.915-148.349), performance status 0-1 (0.007, 11.778, 1.349-102.858), and hemoglobin (0.024, 1.768, 1.077-2.904). Multivariate analysis showed significant differences in the presence of fistula (p = 0.036, CI 1.174-125.825). The odds ratio was 12.154. The mortality rate was 3.8% for non-fistulous empyema and 44.4% for fistulous empyema. In 6 of 9 cases of fistulous empyema, the fistula could be closed. CONCLUSION: Fistula was a significant independent prognostic factor for pneumonia-associated pleural effusions and empyema caused by common bacteria.
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The detailed mechanisms of COVID-19 infection pathology remain poorly understood. To improve our understanding of SARS-CoV-2 pathology, we performed a multi-omics and correlative analysis of an immunologically naïve SARS-CoV-2 clinical cohort from blood plasma of uninfected controls, mild, and severe infections. Consistent with previous observations, severe patient populations showed an elevation of pulmonary surfactant levels. Intriguingly, mild patients showed a statistically significant elevation in the carnosine dipeptidase modifying enzyme (CNDP1). Mild and severe patient populations showed a strong elevation in the metabolite L-cystine (oxidized form of the amino acid cysteine) and enzymes with roles in glutathione metabolism. Neutrophil extracellular traps (NETs) were observed in both mild and severe populations, and NET formation was higher in severe vs. mild samples. Our correlative analysis suggests a potential protective role for CNDP1 in suppressing PSPB release from the pulmonary space whereas NET formation correlates with increased PSPB levels and disease severity. In our discussion we put forward a possible model where NET formation drives pulmonary occlusions and CNDP1 promotes antioxidation, pleiotropic immune responses, and vasodilation by accelerating histamine synthesis.
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We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.
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Nocardiosis is a relatively rare opportunistic infection, ranging from localized to systemic diseases, commonly occurring in immunocompromised patients with high mortality rates. We present a case of a 61-year-old man who received medical treatment for type 2 diabetes mellitus and underwent a physical examination that showed abnormal chest shadows on radiography. Chest computed tomography revealed bronchiectasis and infiltration in the left lower lobe. Nocardia spp. was detected in the bronchial washes, and he was started on sulfamethoxazole-trimethoprim under the diagnosis of pulmonary nocardiosis. 16S ribosomal RNA gene sequencing analysis identified the species as Nocardia cyriacigeorgica. His pulmonary lesions successfully improved after treatment for six months. Pulmonary nocardiosis often presents with symptoms such as hemoptysis and blood-tinged sputum, and bronchiectasis has been identified as an underlying condition. Even in hosts without underlying immunocompromising conditions, Nocardia spp. can be a causative microorganism of pulmonary infections, and it should be considered in the differential diagnoses.
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Background As far as we know, there are no reports comparing the safety and cough frequency of transnasal bronchoscopy (TNB) with transoral bronchoscopy (TOB). Methods The subjects were 50 patients who underwent either TNB or TOB and completed the pain score questionnaire between May and November 2020. Complications, pain scores, and cough frequency (times per minute) were compared between the patients with TNB and TOB. A surgical mask was worn over the mouthpiece during the examination. Results Thirty-two and 18 patients underwent TNB and TOB, respectively. Between the two groups, there were no significant differences in examination time and frequency of serious complications. In pain scores, there were no significant differences in terms of anesthesia suffering, several pains during the examination, and availability of re-examination. The TNB group did not feel the prolonged examination time compared to the TOB group (p=0.04). Cough frequency was lower in the TNB group than in the TOB group (0.36 vs 0.73, p=0.027). Moreover, cough frequency in the 25 TNB patients who underwent thin bronchoscopy was significantly lower (0.19 vs 0.73, p<0.01). Conclusions TNB with a surgical mask was well tolerated and safe. Cough frequency in the transnasal thin bronchoscopy was extremely low, suggesting aerosol reduction can be expected.
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Coronavirus disease (COVID-19) has spread dramatically worldwide. Nafamostat mesylate inhibits intracellular entry of the novel severe acute respiratory syndrome coronavirus 2 and is believed to have therapeutic potential for treating patients with COVID-19. In this study, patients with moderate COVID-19 who were admitted to our hospital were retrospectively analyzed. Thirty-one patients received monotherapy with nafamostat mesylate, and 33 patients were treated conservatively. Nafamostat mesylate was administered with continuous intravenous infusion for an average of 4.5 days. Compared with the conservative treatment, nafamostat mesylate did not improve outcomes or laboratory data 5 days after admission. In addition, no significant differences in laboratory data 5 days after admission and outcomes in high-risk patients were observed. The incidence of hyperkalemia was significantly higher in the nafamostat mesylate group; however, none of the patients required additional treatment. In conclusion, monotherapy with nafamostat mesylate did not improve clinical outcomes in patients with moderate COVID-19. This study did not examine the therapeutic potential of combining nafamostat mesylate with other antiviral agents, and further investigation is required. Because of the high incidence of hyperkalemia, regular laboratory monitoring is required during the use of nafamostat mesylate.
Assuntos
Tratamento Farmacológico da COVID-19 , Hiperpotassemia , Antivirais/uso terapêutico , Benzamidinas , Guanidinas , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Estudos RetrospectivosRESUMO
Fistula formation is an uncommon but serious therapeutic complication of pyothorax-associated lymphoma (PAL) because it decreases the quality of life in patients. Furthermore, a collapsed lung may predispose to pneumonia. In PAL, the lesions might invade the skin and optimal irradiation dose, region, and timing should be carefully determined.