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An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan.
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COVID-19/patologia , Interleucina-8/sangue , Células Supressoras Mieloides/imunologia , Neutrófilos/imunologia , SARS-CoV-2/imunologia , Humanos , Interleucina-8/imunologia , Japão , Contagem de Leucócitos , Células Mieloides/imunologia , Ativação de Neutrófilo/imunologiaRESUMO
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-producing lung cancer induces severe inflammation and a high white blood cell (WBC) count and is associated with poor prognosis. A recent case of G-CSF-producing lung adenocarcinoma showed high expression of programmed cell death ligand 1 (PD-L1) and was treated with pembrolizumab as first-line therapy, which was extremely effective. We hypothesized that G-CSF-producing lung cancers are associated with high PD-L1 expression. METHODS: This retrospective study included patients diagnosed with lung cancer at Yokohama Municipal Citizen's Hospital (Kanagawa, Japan) between 2009 and 2019. The PD-L1 status of 13 patients with high plasma G-CSF levels (≥40 pg/mL) was assessed by conducting immunohistochemical analysis of tissue samples. RESULTS: Of the total patients, 11 were men and 2 were women, with a median age of 74 years (70-85 years). Four, five, and three patients had adenocarcinoma, squamous cell carcinoma, and others, respectively. The median G-CSF level and WBC count were 85.5 pg/mL (range, 40.8-484 pg/mL) and 15,550/µL (range, 6,190-56,800/µL), respectively. The PD-L1 tumor proportion scores (TPSs) were ≥50%, 1%-49%, and <1% in 9, 1, and 3 patients, respectively. The median overall survival time was 7.3 months. Pembrolizumab was administered in six patients as first-line treatment, with two patients showing partial response, one patient with stable disease, and three patients with progressive disease. All six patients had a PD-L1 TPS of ≥50%. CONCLUSION: G-CSF-producing lung cancers may be associated with increased PD-L1 expression. Although immune checkpoint inhibitors are an important treatment option for G-CSF-producing tumors, their effects are limited.
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Antígeno B7-H1/metabolismo , Neoplasias Pulmonares , Idoso , Apoptose , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Ligantes , Masculino , Estudos RetrospectivosRESUMO
Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome.
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COVID-19 , Linfoma de Célula do Manto , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Rituximab/uso terapêutico , SARS-CoV-2RESUMO
BACKGROUND: Vaccination is one of the most important tools to control the COVID-19 pandemic. However, there is little information on the antibody response in humans after the COVID-19 vaccination. METHODS: This single-center, prospective study was conducted in Yokohama, Japan. We included health care workers who had received two doses of COVID-19 vaccination (BNT162b2) 21 days apart. We measured serum immunoglobulin G (IgG) to nucleoprotein and spike protein of SARS-CoV-2 with commercially available kits before and 7, 14, and 35 days after the first dose of vaccination. RESULTS: A total of 104 workers participated in this study. Of these, 7 participants were seropositive with antibodies to spike protein at baseline and 4 of the 7 seropositive participants had COVID-19 history. The mean level of IgG to spike protein (QT) was 45.2, 1219, 2845, and 23489 AU/mL at baseline, on days 7, 14, and 35, respectively, although the values for nucleoprotein (NG) were 0.2, 0.21, 0.22, and 0.19 S/C, respectively. On day 7, QT in seropositive participants at baseline was elevated, whereas it was not elevated in seronegative participants at baseline until day 14. CONCLUSIONS: QT was elevated over the cutoff in all the participants at day 35, but NG did not change between baseline and day 35.
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Vacinas contra COVID-19 , COVID-19 , Anticorpos Antivirais , Formação de Anticorpos , Vacina BNT162 , Pessoal de Saúde , Humanos , Japão , Pandemias , Estudos Prospectivos , SARS-CoV-2RESUMO
BACKGROUND: Compared with standard chemotherapy, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are more effective in patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, data comparing the efficacies of different EGFR-TKIs, especially regarding the presence of brain metastasis, are lacking. METHODS: EGFR-TKI naive patients with recurrent or stage IIIB/IV NSCLC harboring EGFR mutations, excluding resistance mutations, were enrolled in this study. We retrospectively determined progression-free survival (PFS) using the Kaplan-Meier method with log-rank test in patients treated with either gefitinib or erlotinib, cumulative incidence of central nervous system (CNS) progression using the Fine and Gray competing risk regression model, and favorable prognostic factors for CNS progression by multivariate analysis. RESULTS: Seventy-seven EGFR-TKI-naive patients were started on either gefitinib (n = 55) or erlotinib (n = 22) in our hospital from April 2010 to April 2016. Among the patients with brain metastasis, PFS tended to be longer in the erlotinib than in the gefitinib group. In the analysis of cumulative incidence, the probability of CNS progression was lower in the erlotinib group than in the gefitinib group. Particularly, in a subgroup analysis of the patients with brain metastasis, there was a significant difference between the erlotinib and gefitinib groups (hazard ratio 0.25; 95% confidence interval, 0.08-0.81; p = 0.021). Of the prognostic factors for CNS progression evaluated, the absence of brain metastasis before EGFR-TKI therapy and receiving erlotinib (vs gefitinib) had a significantly favorable effect on patient prognosis. CONCLUSION: Although this was a retrospective analysis involving a small sample size, erlotinib is potentially more promising than gefitinib for treatment of brain metastasis in patients with EGFR-mutant NSCLC.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , PrognósticoRESUMO
BACKGROUND: Cold agglutination syndrome is a subtype of autoimmune hemolytic anemia. The condition is referred to as "cold" because the antibodies become active and induce hemolysis at cold temperatures, typically 3-4 °C, which is not always the case in other kinds of autoimmune hemolytic anemia. Whereas primary cold agglutination syndrome may occur in the absence of underlying conditions, secondary cold agglutination syndrome is associated with the presence of underlying infections, including coronavirus disease 2019. CASE PRESENTATION: We report the case of a 69-year-old Japanese woman with periodontitis who was referred to our hospital with complaints of brown-colored urine and chest pain. Her hemoglobin level was 6.1 g/dL. Computed tomography revealed multiple lung abscesses. Her direct antibody test results were positive (2+) for anti-complement direct antiglobulin and negative for immunoglobulin G, and her cold agglutinin titer was elevated at 1:4096. Workup for anemia revealed a positive result for cold agglutination syndrome. The patient had received the fourth dose of coronavirus disease 2019 vaccination. Nasopharyngeal swab test for detecting severe acute respiratory syndrome coronavirus 2 using a real-time reverse-transcription polymerase chain reaction gave a cycle threshold value of 42.3, and the level of virus-specific immunoglobulin G was elevated at 7.71 S/C (normal range -1.4 S/C). CONCLUSION: A decrease in hemoglobin in patients with coronavirus disease 2019 may be associated with secondary cold agglutination syndrome. The patient was hypothesized to have developed multiple lung abscesses with secondary cold agglutination syndrome following coronavirus disease 2019. Thus, following coronavirus disease 2019, patients can develop secondary cold agglutination syndrome, which could worsen owing to associated bloodstream bacterial infections.
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Anemia Hemolítica Autoimune , COVID-19 , Abscesso Pulmonar , SARS-CoV-2 , Humanos , Feminino , Idoso , COVID-19/complicações , COVID-19/diagnóstico , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/etiologia , Abscesso Pulmonar/etiologia , Tomografia Computadorizada por Raios XRESUMO
Persistent inflammation in chronic HIV infection may affect immune responses against SARS-CoV-2 infection. Plasma levels of multiple proinflammatory cytokines during acute SARS-CoV-2 infection were assessed in people with HIV (PWH) with effective cART. There were no significant differences in any of the tested cytokines between COVID-19 severity in PWH, while most of them were significantly higher in individuals with severe disease in HIV-uninfected individuals, suggesting that excess cytokines release by hyper-inflammatory responses does not occur in severe COVID-19 with HIV infection. The strong associations between the cytokines observed in HIV-uninfected individuals, especially between IFN-α/TNF-α and other cytokines, were lost in PWH. The steady state plasma levels of IP-10, ICAM-1, and CD62E were significantly higher in PWH, indicating that PWH are in an enhanced inflammatory state. Loss of the several inter-cytokine correlations were observed in in vitro LPS stimuli-driven cytokines production in PWH. These data suggest that inflammatory responses during SARS-CoV-2 infection in PWH are distinct from those in HIV-uninfected individuals, partially due to the underlying inflammatory state and/or impairment of innate immune cells.
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BACKGROUND: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT. METHODS: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateâ , moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated. RESULTS: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity. CONCLUSION: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan.
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COVID-19 , Pulmão , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , COVID-19/complicações , COVID-19/diagnóstico por imagem , COVID-19/epidemiologia , Dispneia/etiologia , População do Leste Asiático , Japão/epidemiologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Alta do Paciente , Estudos Prospectivos , Testes de Função Respiratória , Índice de Gravidade de Doença , Sociedades Médicas , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The relationship between epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance, including osimertinib, and programmed cell death-ligand 1 (PD-L1) expression status in EGFR-mutated non-small cell lung carcinoma (NSCLC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 64 patients with unresectable advanced or metastatic NSCLC carrying EGFR exon 19 deletions (ex19del) or EGFR exon 21 L858R substitutions (L858R) who received osimertinib as the first-line treatment. We compared progression-free survival (PFS) between eligible patients with PD-L1 tumor proportion scores (TPS) ≥20% and PD-L1 TPS <20% using the Kaplan-Meier survival plots with a log-rank test. Multivariate analysis was performed to examine the poor prognostic factors of PFS. RESULTS: The PD-L1 TPS ≥20% group included 22 cases (median [range] age: 70.5 [33-86] years; 10 women [45.5%]; 11 current or ex-smokers [50%]); ECOG performance status (PS) of 0-1/2/3/4 was noted in 16/4/1/1 patients, respectively. The PD-L1 TPS <20% group included 42 patients (median [range] age 73 [43-88] years; 29 women [69%]; 12 current or ex-smokers [28.6%]); ECOG PS of 0-1/2/3/4 was noted in 33/6/3/0 cases, respectively. The median PFS was 9.1 and 28.1 months in the PD-L1 TPS ≥20% and PD-L1 TPS <20% groups, respectively (log-rank p = 0.013). Multivariate analysis revealed that PD-L1 TPS ≥20% was associated with PFS (hazard ratio: 2.35, 95% confidence interval: 1.09-5.08, p = 0.030). CONCLUSION: PD-L1 TPS ≥20% in patients with EGFR-mutated NSCLC may be associated with early resistance to osimertinib.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estudos Retrospectivos , Receptores ErbB , Mutação , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood. Peripheral blood mononuclear cells from COVID-19 patients were collected longitudinally, and single-cell transcriptome and T cell receptor repertoire analysis was performed. Comparison of molecular features and patients' clinical information revealed that the proportions of cells present, and gene expression profiles differed significantly between mild and severe cases; although even among severe cases, substantial differences were observed among the patients. In one severely-infected elderly patient, an effective antibody response seemed to have failed, which may have caused prolonged viral clearance. Naïve T cell depletion, low T cell receptor repertoire diversity, and aberrant hyperactivation of most immune cell subsets were observed during the acute phase in this patient. Through this study, we provided a better understanding of the diversity of immune landscapes and responses. The information obtained from this study can help medical professionals develop personalized optimal clinical treatment strategies for COVID-19.
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COVID-19 , Humanos , Idoso , SARS-CoV-2 , Leucócitos Mononucleares , Japão/epidemiologia , Análise de Célula Única , Receptores de Antígenos de Linfócitos TRESUMO
Introduction: C-ros oncogene 1 (ROS1) translocation is an oncogenic driver-mutation identified in 1-2% of non-small-cell lung cancer (NSCLC) cases. Although crizotinib, a tyrosine kinase inhibitor (TKI) against ALK/ROS1, is known to be effective against ROS1-fusion-positive NSCLC, such cases sometimes progress with brain metastases. The most frequently reported crizotinib-resistance mutation is ROS1 G2032R, and some studies have found that even newly developed ROS1 TKIs, such as entrectinib and lorlatinib, show a decreased efficacy against it. The optimal therapies for ROS1-fusion-positive NSCLC and how such cases can be sequenced have not yet been established. Case Presentation: We herein report a patient with ROS1-fusion-positive NSCLC diagnosed at 34 years old. Crizotinib was started at the diagnosis and switched after 25 months to cisplatin/pemetrexed/bevacizumab once the disease progressed with multiple brain metastases that were resistant to stereotactic radiation therapy. The cytotoxic chemotherapy stabilized the patient's condition for 17 months until he developed leptomeningeal metastasis (LM). He underwent lumboperitoneal shunting and whole-brain radiotherapy, followed by crizotinib re-administration. Despite crizotinib treatment, his neurological symptoms, such as double vision, headache, weakness in the legs, and walking difficulties, progressed. Eventually, subsequent entrectinib treatment was initiated, which resolved all of the symptoms mentioned above. Regrettably, liquid next-generation sequencing had failed to detect the resistance mechanism due to minimal ctDNA in this case. Conclusion: These findings imply that sequential entrectinib administration may be effective in patients with disease progression limited to central nervous system metastases during crizotinib administration.
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We report the first case with COVID-19-like acute respiratory distress syndrome after mRNA-1273 SARS-CoV-2 vaccination. An 88-year-old woman developed dyspnea several hours after vaccination with the second dose of mRNA-1273. She was hospitalized on day nine due to worsening dyspnea. Chest computed tomography showed bilateral ground-glass opacities and consolidations, mainly in the peripheral lung areas. Repeat polymerase chain reaction tests for SARS-CoV-2 were negative, although the serum level of antibodies against spike protein was extremely elevated. Her condition did not improve with high-dose corticosteroids and high-flow nasal cannula oxygen therapy; she died on day 18. Autopsy findings revealed very early-phase diffuse alveolar damage in the whole lung without other lung diseases. The clinical and pathological findings suggested vaccine-induced acute respiratory distress syndrome. Serological and pathological tests might be useful to differentiate the disease from COVID-19.
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COVID-19 , Síndrome do Desconforto Respiratório , Vacina de mRNA-1273 contra 2019-nCoV , Idoso de 80 Anos ou mais , Autopsia , Vacinas contra COVID-19/efeitos adversos , Dispneia , Feminino , Humanos , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2 , VacinaçãoRESUMO
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare manifestation of malignancy. The antemortem diagnosis is difficult, since patients present with rapidly progressive symptoms. We recently observed a case of PTTM following lymphedema of the lower extremities. We did not reach a diagnosis, even after performing BAL and TBLB. The patient manifested pulmonary hypertension and died on the 9th day of admission. Autopsy revealed a tumor embolism in the pulmonary arterioles accompanied by fibrocellular epithelial cell proliferation, but the primary organ was not identified. To our knowledge, this is the first reported case of PTTM with lymphedema.
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Remdesivir has been shown to reduce recovery time and mortality among patients with coronavirus disease 2019 (COVID-19). However, data regarding the efficacy and safety of remdesivir use are limited in Japan. We conducted a single-center retrospective cohort study at Yokohama Municipal Citizen's Hospital, Kanagawa, Japan. Patients with COVID-19 pneumonia treated with remdesivir were included. The onset of acute pancreatitis and increased pancreatic enzyme levels and clinical, laboratory, treatment, and outcome data were collected and analyzed. A total of 201 patients were included. Among the 201 patients treated with remdesivir, 177 recovered from COVID-19. Increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis developed in 23 of the 201 patients. The potential etiopathogenetic effects of remdesivir on increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis were ascertained by reviewing the characteristics of patients hospitalized for COVID-19 who did not receive remdesivir treatment. Only 3 of 159 patients had increased pancreatic enzyme levels of grade 3 or higher during the treatment course. Multivariate analysis indicated remdesivir administration and severe COVID-19 infection by National Institute of Health standards as independent risk factors. Acute pancreatitis and severe increases in pancreatic enzyme levels were observed among patients with COVID-19 treated with remdesivir.
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Tratamento Farmacológico da COVID-19 , Pancreatite , Doença Aguda , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Humanos , Pancreatite/tratamento farmacológico , Estudos RetrospectivosRESUMO
Malignant pericardial mesothelioma (MPM) is a rare tumour that arises from the mesothelial cells of the pericardium. No standard treatment has been established owing to a poor treatment response; therefore, MPM has a poor prognosis. We herein report a rare case of MPM in a 70-year-old man that was diagnosed immunohistopathologically using cell block sections of pericardial fluid and in which long-term survival for more than 3 years was achieved with only periodic pericardial drainage. Immunohistopathological staining investigations, especially BRCA1-associated protein 1 (BAP1) immunostaining using cell block sections of pericardial effusion, are effective in making a diagnosis of MPM. Well-differentiated papillary mesothelioma (WDPM) with BAP1 loss progresses to MPM in the long term, showing that BAP1 loss may induce phenotypical evolution of WDPM. BAP1 loss may also progress to malignant mesothelioma in situ and then to invasive mesothelioma. BAP1 immunohistochemistry should be considered for the early diagnosis of MPM.
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We report an acute clinical course of pneumonia caused by Legionella pneumophila in a patient receiving chemotherapy for lung cancer and corticosteroid therapy. A 57-year-old man presented with fever and dyspnoea and was admitted to our hospital. Chest computed tomography revealed a new left lower lung infiltrate, tumour progression in the right upper lung region, metastases to lymph nodes and pleural effusion. The urinary antigen test for Legionella was positive. The patient's oxygen requirement increased on the day of admission, and he died the day after hospitalization. Legionnaires' disease may manifest with an acute presentation, and patients in Japan with physical risk factors for this disease could get infected despite the absence of environmental risk factors. Early treatment for suspected Legionnaire's disease should be considered.
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Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is useful for diagnosing hilar and mediastinal lymph node enlargement; however, specimens obtained are often small and inadequate for pathologic diagnosis. In June 2017, EchoTip ProCore, a puncture needle with a side trap, was launched in Japan. In this single-center prospective interventional study, 57 patients with lymph nodes, intrapulmonary tumor or pleural mass were diagnosed using EBUS-TBNA with EchoTip ProCore between June 2017 and February 2020. EBUS-TBNA was performed for 57 patients and 53 patients had sufficient specimen for histologic diagnosis. The following pathologic subtypes were diagnosed: non-small cell lung cancer, 22; small cell lung cancer, 8; cancer of unknown primary, 2; neuroendocrine tumor (G2) recurrence, 1; lymphoma, 2; metastatic renal cell carcinoma, 3; thymoma recurrence, 1; sarcoidosis, 4; tuberculosis, 1; and non-malignancy, 9. In addition, the cytology showed Class V in 31 out of 57 cases (54.4%). In total, a definitive pathological diagnosis was obtained in 50 out of 57 cases (87.7%). The only complication was pneumonia caused by BAL simultaneously combined with EBUS-TBNA in one patient. Among 13 patients with inadequate specimens or without malignancy, only one patient was subsequently diagnosed with malignancy, and the median follow-up period was 300 days. EBUS-TBNA using EchoTip ProCore can obtain a sufficient specimen size for pathologic diagnosis.
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Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems. METHODS: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development. RESULTS: Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 µg/mL vs. 1.28 µg/mL; p = 0.015), lower values of lymphocyte (median, 802/µL vs. 1007/µL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001). CONCLUSION: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71.
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Teste de Ácido Nucleico para COVID-19/normas , COVID-19/diagnóstico , RNA Viral/análise , Idoso , Biomarcadores/análise , COVID-19/mortalidade , Teste de Ácido Nucleico para COVID-19/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/virologia , Admissão do Paciente , Prognóstico , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Carga ViralRESUMO
HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.57-8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID-19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID-19.
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COVID-19 , Cadeias HLA-DRB1 , Alelos , COVID-19/diagnóstico , COVID-19/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Cadeias HLA-DRB1/genética , HumanosRESUMO
BACKGROUND/AIM: We assessed the efficacy of immune checkpoint inhibitors (ICIs) in older patients because of the limited information regarding these patients. PATIENTS AND METHODS: We retrospectively analyzed 66 consecutive patients ≥70 years old with advanced non-small cell lung cancer (NSCLC). A total of 31 patients received ICIs (ICIs group) and 35 patients received only cytotoxic regimens (No ICIs group). RESULTS: Patients with squamous cell carcinoma who received ICIs had better overall survival (OS) than those who did not (9.7 versus 4.7 months, p=0.027). In multivariate analysis, treatment with ICIs [hazard ratio (HR)=0.54, 95% confidence interval (CI)=0.30-0.98, p=0.044], good performance status (HR=0.30, 95%CI=0.16-0.57, p=0.0003), and histology other than squamous cell carcinoma (HR=0.41, 95%CI=0.19-0.83, p=0.014) were significantly favorable factors for OS. CONCLUSION: ICIs may be effective for older patients with NSCLC, especially squamous cell carcinoma patients.