RESUMO
PURPOSE: Despite the importance of abscess lesions in clinical decisions regarding anaerobic bacteremia (AB), their impact on clinical characteristics remains unclear. Herein, we aimed to elucidate the clinical factors associated with AB that were unaccompanied by detectable abscess lesions during the initial phase of infection. METHODS: This was a multicenter retrospective observational study involving patients with culture-proven AB at six tertiary hospitals in Japan between January 2012 and March 2022. Data on clinical characteristics, laboratory and radiological findings were collected, and their associations with the absence of detectable abscess lesions were analyzed. RESULTS: In total, 393 participants were included. Abscess lesions were absent in 42.7% of the entire cohort and detectable in the remaining patients. No differences were identified in the malignancy, severity, or 30-day mortality between patients with and without detectable abscess lesions. Multivariate logistic regression analysis adjusted for age and the modified Charlson comorbidity score revealed that the immunosuppressive status (febrile neutropenia or corticosteroid use), C-reactive protein (CRP) level ≤9.8 mg/dL at onset, and the presence of gram-positive anaerobic rods (GPARs) were independently associated with AB unaccompanied by detectable abscess lesions [odds ratios (ORs) 3.24, 3.00, and 2.81, respectively; p < 0.05]. CONCLUSION: This study elucidated distinctive clinical and microbiological characteristics of AB unaccompanied by detectable abscess lesions, with relatively lower CRP elevation, immunosuppressive status, and GPARs as the causative anaerobes.
RESUMO
BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.
Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Feminino , Masculino , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Pneumonia/diagnóstico , Pneumonia/microbiologia , Pneumonia/tratamento farmacológico , Pneumonia/mortalidade , Estudos Prospectivos , Fatores de Risco , Antibacterianos/uso terapêutico , Valor Preditivo dos Testes , Demência/diagnóstico , Demência/epidemiologiaRESUMO
BACKGROUND: Aortic stenosis (AS) and aortic valve calcification (AVC) are occasionally observed in patients receiving maintenance dialysis. However, their prevalence and factors associated with them in patients undergoing dialysis remain unknown. We aimed to elucidate the aortic valve status at the time of dialysis initiation and patient prognosis based on aortic valve status. METHODS: We analyzed 289 patients initiating dialysis (hemodialysis: peritoneal dialysis = 275:14) between 2016 and 2023. "AS and/or AVC" was detected using echocardiography. AS was defined as a maximum transaortic velocity > 2.0 m/s. Statistical analyses including multivariable logistic regression and Cox regression were used to assess the association between patient characteristics and survival outcomes. RESULTS: Aortic valve changes were observed in 121 (42%) patients, among which 33 (11%) met the AS criteria. The mean age of patients in the AS, AVC without AS, and control groups was 79.1 ± 8.9, 75.9 ± 9.2, and 68.3 ± 12.9, respectively (P < 0.001). Multivariable logistic regression models showed that only age was associated with aortic valve changes (P < 0.001). Age and other important factor-adjusted multivariable Cox regression models showed that AS was an independent risk factor for death after dialysis initiation (hazard ratio (HR): 1.95, 95% confidence interval (CI): 1.06 - 3.59, P = 0.04). However, aortic valve changes ("AS and/or AVC") were not a risk factor for death (HR: 1.51, 95% CI 0.95 - 2.39, P = 0.08). CONCLUSIONS: With the growing older population undergoing dialysis, aortic valve changes should be closely monitored. Particularly, AS is crucial because of its impact on patient prognosis.
RESUMO
BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.
Assuntos
Bases de Dados Factuais , Paragonimíase , Humanos , Paragonimíase/epidemiologia , Japão/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Tempo de Internação/estatística & dados numéricos , Pneumopatias Parasitárias/epidemiologia , Pneumopatias Parasitárias/parasitologia , Pneumopatias Parasitárias/tratamento farmacológico , Adulto Jovem , Hospitalização/estatística & dados numéricos , Praziquantel/uso terapêutico , Adolescente , Animais , Comorbidade , População do Leste AsiáticoRESUMO
INTRODUCTION: The diagnostic tools of nucleic acid amplification tests and antigen tests have been extensively employed for the detection of Coronavirus disease 2019 (COVID-19). Although the reverse-transcriptase polymerase chain reaction (RT)-PCR test has high sensitivity and specificity, it is a time-consuming and labor-intensive process. On the other hand, antigen tests are simple and prompt, however, their low sensitivity and potential for false positives have been identified as limitations. In light of these factors, the development of novel tests that combine speed and clinical dependability is a promising prospect. METHODS: Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) excites chromophores by means of an enhanced electromagnetic field induced on a gold film surface. It enables the highly sensitive measurement of biomarkers in a short and simple 20-min window. In this study, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) SPFS-based antigen test targeting the SARS-CoV-2 nucleocapsid protein was performed and evaluated in 25 patients with COVID-19 and 10 non-infected controls. RESULTS: A positive correlation was observed between antigen levels determined by SPFS and RNA levels determined via RT-PCR. The sensitivity values were 100 %, 92 %, and 62.5 %; and the specificity values were 100 %, 90 %, and 100 %; for nasopharyngeal swabs, nasal swabs, and saliva specimens when the cutoff values were set to 65.1, 0.2, and 1.5 pg/mL, respectively. No clinically problematic cross-reactivity with analogous coronaviruses was observed. CONCLUSIONS: The SARS-CoV-2 SPFS antigen test showed excellent clinical diagnostic accuracy for nasopharyngeal and nasal swabs, with a rapid turnaround.
RESUMO
BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.
Assuntos
Antibacterianos , Fluoroquinolonas , Pneumonia Associada a Assistência à Saúde , Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Idoso , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/administração & dosagem , Japão , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/microbiologia , Resultado do Tratamento , Administração Oral , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Cryptococcal meningitis (CM) is an invasive fungal infection with a poor prognosis that often occurs in both healthy individuals and compromised hosts, such as patients infected with human immunodeficiency virus (HIV). Unlike CM in HIV patients, evidence regarding CM in non-HIV patients is limited to small retrospective studies. OBJECTIVE: To identify the pretreatment prognostic factors for CM in non-HIV patients. METHODS: We conducted a large retrospective analysis of CM in non-HIV patients using data from a nationwide Japanese database. The study included hospitalized patients diagnosed with CM between 1 April 2010 and 31 March 2017. All-cause mortality was compared between patients with CM with and without HIV infection. Poor diagnostic factors were analysed in the non-HIV CM group. RESULTS: Overall, 533 (64 HIV and 469 non-HIV) patients met the criteria. The mortality rate at 90 days was significantly lower in the HIV group (6.3% vs. 25.4% p = .0002). In a logistic regression analysis of the non-HIV group, age ≥ 65 y (odds ratio [OR] 2.37, 95% CI 1.17-4.78), impaired consciousness (Japan Coma Scale ≥1) (OR 2.25, 95% CI 1.29-3.93), haemodialysis (OR 3.53, 95% CI 1.12-11.20) and previous corticosteroid usage (OR 2.40, 95% CI 1.37-4.19) were associated with poor prognosis at 30 days after diagnosis. CONCLUSION: More caution is suggested when treating non-HIV with CM in older patients with impaired consciousness, previous corticosteroid usage and haemodialysis.
Assuntos
Infecções por HIV , Meningite Criptocócica , Humanos , Idoso , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/complicações , Infecções por HIV/complicações , HIV , Estudos Retrospectivos , Prognóstico , CorticosteroidesRESUMO
BACKGROUND: This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. METHODS: Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. RESULTS: A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5-64.9%; mean age: 35.3-37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. CONCLUSIONS: Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. CLINICAL TRIALS REGISTRATION: Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).
Assuntos
COVID-19 , Epidemias , Humanos , Masculino , Adulto , SARS-CoV-2 , Antivirais/efeitos adversosRESUMO
Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) with a broad coverage against ALK mutations, has demonstrated dramatic effects in patients with ALK-rearranged lung cancer. The mechanisms of acquired resistance to lorlatinib by secondary ALK compound mutations have recently been reported; however, resistance mechanisms other than secondary mutations remain unclear. Here, we investigated the molecular mechanisms of the acquired resistance in ALK-rearranged lung cancer cells in vitro. We established two different lorlatinib-resistant ALK-rearranged lung cancer cell lines (H3122LR and A925LLR) via long-term administration of lorlatinib. These resistant cells did not harbor the secondary ALK mutations and showed cross-resistance to the other kinds of ALK-TKIs (crizotinib or alectinib) compared with the parental cells; however, these resistant cells overexpressed the phosphorylated human epidermal growth factor receptor 3 (HER3) protein and the ligand of HER3 (neuregulin 1; NRG1). Pharmacological inhibition of HER3 with pan-HER inhibitors or genetic knockdown of HER3 with siRNA resensitized H3122LR and A925LLR cells to lorlatinib in vitro, indicating that H3122LR and A925LLR acquired resistance by NRG1/HER3 activation. These findings demonstrated that targeting NRG1/HER3 is a potential novel therapeutic option for lorlatinib-resistant ALK-rearranged lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Lactamas Macrocíclicas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Neuregulina-1/genética , Inibidores de Proteínas QuinasesRESUMO
Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro.
Assuntos
Candida auris , Equinocandinas , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Equinocandinas/genética , Trato Gastrointestinal , Micafungina/farmacologia , Testes de Sensibilidade Microbiana , Mutação/genéticaRESUMO
BACKGROUND: Interstitial lung disease is frequently comorbid with dermatomyositis and has a poor prognosis, especially in patients with the anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody. However, the pathogenesis of dermatomyositis-related interstitial lung disease remains unclear. METHODS: We examined 18 and 19 patients with dermatomyositis-related interstitial lung disease and idiopathic pulmonary fibrosis (control), respectively. Lung tissues obtained from these patients were semi-quantitatively evaluated by immunohistochemical staining with in-house anti-human MDA5 monoclonal antibodies, as well as anti-human immunoglobulin (Ig) G, IgM, IgA, and complement component 3(C3) antibodies. We established human MDA5 transgenic mice and treated them with rabbit anti-human MDA5 polyclonal antibodies, and evaluated lung injury and Ig and C3 expression. RESULTS: MDA5 was moderately or strongly expressed in the lungs of patients in both groups, with no significant differences between the groups. However, patients with dermatomyositis-related interstitial lung disease showed significantly stronger expression of C3 (p < 0.001), IgG (p < 0.001), and IgM (p = 0.001) in the lungs than control. Moreover, lung C3, but IgG, IgA, nor IgM expression was significantly stronger in MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease (n = 9) than in MDA5 autoantibody-negative dermatomyositis-related interstitial lung disease (n = 9; p = 0.022). Treatment with anti-MDA5 antibodies induced lung injury in MDA5 transgenic mice, and strong immunoglobulin and C3 expression was observed in the lungs of the mice. CONCLUSION: Strong immunoglobulin and C3 expression in the lungs involve lung injury related to dermatomyositis-related interstitial lung disease. Enhanced immune complex formation in the lungs may contribute to the poor prognosis of MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease.
Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Lesão Pulmonar , Animais , Humanos , Camundongos , Complexo Antígeno-Anticorpo , Autoanticorpos , Dermatomiosite/genética , Dermatomiosite/complicações , Progressão da Doença , Imunoglobulina A , Imunoglobulina M , Helicase IFIH1 Induzida por Interferon/genética , Pulmão , Doenças Pulmonares Intersticiais/etiologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: We conducted a multicenter study to evaluate the performance of a novel fully automated molecular point-of-care test using transcription-reverse transcription concerted reaction that can detect influenza A and B within 15 min in nasopharyngeal swabs and gargle samples (TRCsatFLU). METHODS: Patients who visited or were hospitalized at eight clinics and hospitals with influenza-like illnesses between December 2019 and March 2020 participated in this study. We collected nasopharyngeal swabs from all patients and gargle samples from patients whom the physician judged fit to perform gargling. The result of TRCsatFLU was compared to a conventional reverse transcription-polymerase chain reaction (RT-PCR). If the results of TRCsatFLU and conventional RT-PCR were different, the samples were analyzed by sequencing. RESULTS: We evaluated 233 nasopharyngeal swabs and 213 gargle samples from 244 patients. The average age of the patients was 39.3 ± 21.2. Of the patients, 68.9% visited a hospital within 24 h of symptom onset. The most common symptoms were fever (93.0%), fatigue (79.5%), and nasal discharge (64.8%). All patients in whom the gargle sample was not collected were children. Influenza A or B was detected in 98 and 99 patients in nasopharyngeal swabs and gargle samples using TRCsatFLU, respectively. Four and five patients in nasopharyngeal swabs and gargle samples, respectively, with different TRCsatFLU and conventional RT-PCR results. Influenza A or B was detected using sequencing in all samples with different results. Based on the combined conventional RT-PCR and sequencing results, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TRCsatFLU for influenza detection in nasopharyngeal swabs were 0.990, 1.000, 1.000, and 0.993, respectively. In the gargle samples, the sensitivity, specificity, PPV, and NPV of the TRCsatFLU for detecting influenza were 0.971, 1.000, 1.000, and 0.974, respectively. CONCLUSIONS: The TRCsatFLU showed great sensitivity and specificity for the detection of influenza in nasopharyngeal swabs and gargle samples. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (reference number: UMIN000038276) on October 11, 2019. Before sample collection, written informed consent for the participation and publication of this study was obtained from all participants.
Assuntos
Influenza Humana , Criança , Humanos , Febre , Hospitais , Testes ImediatosRESUMO
Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan.
Cryptococcus neoformans strains obtained from non-human immunodeficiency virus-infected patients were observed to maintain good antifungal susceptibility to fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine over a 25-year-long period in Nagasaki, Japan.
RESUMO
BACKGROUND: A test-based strategy against coronavirus disease 2019 (COVID-19) is one of the measures to assess the need for isolation and prevention of infection. However, testing with high sensitivity methods, such as quantitative RT-PCR, leads to unnecessary isolation, whereas the lateral flow antigen test shows low sensitivity and false negative results. The purpose of this study was to evaluate the performance of the LumiraDx SARS-CoV-2 Ag test (Lumira Ag), a rapid microfluidic immunofluorescence method, in assessing infectivity. METHODS: This study was performed from March 2022 to July 2022. A pair of nasopharyngeal swab samples were obtained from each patient with mild COVID-19. One swab was used for Lumira Ag testing, and the other for quantitative RT-PCR testing and virus culture. RESULTS: A total of 84 patients were included in the study. Among them, PCR, Lumira Ag test, and virus culture indicated positivity for 82, 66, and 24 patients, respectively. When comparing the Lumira Ag test to virus culture, its sensitivity was 100.0% (24/24), specificity, 30.0% (18/60); positive predictive value, 36.3% (24/66); and negative predictive value (NPV), 100.0% (18/18). The positive sample for virus culture was observed until the ninth day from the onset of symptoms, while the Lumira Ag test was observed until day 11. CONCLUSIONS: The Lumira Ag test showed high sensitivity and NPV (100% each) compared to virus culture. A test-based strategy using the Lumira Ag test can effectively exclude COVID-19 infectiousness.
Assuntos
COVID-19 , Microfluídica , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Imunofluorescência , Testes Imunológicos , Sensibilidade e Especificidade , Antígenos ViraisRESUMO
BACKGROUND: Anti-glomerular basement membrane (anti-GBM) nephritis, characterized by glomerular crescent formation, requires early treatment because of poor prognosis. Hydroxychloroquine (HCQ) is an antimalarial drug with known immunomodulatory, anti-inflammatory, and autophagy inhibitory effects; it is recognized in the treatment of autoimmune diseases such as systemic lupus erythematosus. However, its effect on anti-GBM nephritis remains unknown. In this study, we investigated the effect of HCQ on anti-GBM nephritis in rats. METHODS: Seven-weeks-old male WKY rats were administered anti-GBM serum to induce anti-GBM nephritis. Either HCQ or vehicle control was administered from day 0 to day 7 after the induction of nephritis. Renal function was assessed by measuring serum creatinine, proteinuria, and hematuria. Renal histological changes were assessed by PAS staining and Masson trichrome staining, and infiltration of macrophages was assessed by ED-1 staining. Mitogen-activated protein kinase (MAPK) was evaluated by western blotting, while chemokine and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay using urine sample. RESULTS: HCQ treatment suppressed the decline in renal function. Histologically, extracapillary and intracapillary proliferations were observed from day 1, while fibrinoid necrosis and ED-1 positive cells were observed from day 3. Rats with anti-GBM nephritis showed high levels of monocyte chemotactic protein-1 and tumor necrosis factor-α. These changes were significantly suppressed following HCQ treatment. In addition, HCQ suppressed JNK/p38 MAPK phosphorylation. CONCLUSION: HCQ attenuates anti-GBM nephritis by exerting its anti-inflammatory effects via the inhibition of JNK/p38 MAPK activation, indicating its therapeutic potential against anti-GBM nephritis.
Assuntos
Glomerulonefrite , Nefrite , Ratos , Masculino , Animais , Proteínas Quinases p38 Ativadas por Mitógeno , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Ratos Endogâmicos WKY , Nefrite/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Glomerulonefrite/patologiaRESUMO
BACKGROUND: Hyperkalemia and hypokalemia are associated with mortality in patients undergoing hemodialysis. However, there are few reports on the association between potassium level fluctuations and mortality. We retrospectively investigated the association between serum potassium level variability and mortality in patients undergoing hemodialysis. METHODS: This study was conducted at a single center. Variability in serum potassium levels was evaluated using the standard deviation of potassium level from July 2011 to June 2012, and its association with prognosis was examined by following up the patients for 5 years. Serum potassium variability was assessed as the coefficient of variation, and the statistical analysis was performed after log transformation. RESULTS: Among 302 patients (mean age 64.9 ± 13.3; 57.9% male; and median dialysis vintage 70.5 months [interquartile range, IQR 34-138.3]), 135 died during the observation period (median observation period 5.0 years [2.3-5.0]). Although the mean potassium level was not associated with prognosis, serum potassium level variability was associated with prognosis, even after adjustments for confounding factors such as age and dialysis time (hazard ratio: 6.93, 95% confidence interval [Cl] 1.98-25.00, p = 0.001). After the adjustments, the coefficient of variation of potassium level in the highest tertile (T3) showed a higher relative risk for prognosis than that in T1 (relative risk: 1.98, 95% CI 1.19-3.29, p = 0.01). CONCLUSIONS: Variability in serum potassium levels was associated with mortality in patients undergoing hemodialysis. Careful monitoring of potassium levels and their fluctuations is necessary for this patient population.
Assuntos
Hipopotassemia , Diálise Renal , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Potássio , Hipopotassemia/etiologia , PrognósticoRESUMO
INTRODUCTION: Sequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23. METHODS: Patients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed. RESULTS: The study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period. CONCLUSIONS: Patients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group.
RESUMO
A 65-year-old Japanese woman repeatedly withdrew and resumed antibiotics against pulmonary non-tuberculous mycobacterial infection caused by Mycobacterium intracellulare for more than 10 years. Although she continued to take medications, her respiratory symptoms and chest computed tomography indicated an enlarged infiltrative shadow in the lingular segment of the left lung that gradually worsened over the course of a year or more. Bronchoscopy was performed and mycobacterial culture of the bronchial lavage fluid was negative, whereas Exophiala dermatitidis was detected. After administration of oral voriconazole was initiated, the productive cough and infiltrative shadow resolved. There are no characteristic physical or imaging findings of E. dermatitidis, and it often mimics other chronic respiratory infections. Thus, when confronting refractory non-tuberculous mycobacterial cases, it might be better to assume other pathogenic microorganisms, including E. dermatitidis, and actively perform bronchoscopy.
Assuntos
Exophiala , Feoifomicose , Pneumonia , Humanos , Feminino , Idoso , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico , Feoifomicose/microbiologia , Micobactérias não Tuberculosas , Voriconazol/uso terapêutico , Pneumonia/tratamento farmacológico , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
OBJECTIVES: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses. PATIENTS AND METHODS: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT). RESULTS: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole. CONCLUSIONS: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.
Assuntos
Aspergilose , Criptococose , Infecções Fúngicas Invasivas , Mucormicose , Aspergilose Pulmonar , Humanos , Voriconazol/efeitos adversos , Mucormicose/tratamento farmacológico , Japão , Triazóis/efeitos adversos , Antifúngicos/efeitos adversos , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Aspergilose Pulmonar/tratamento farmacológico , Criptococose/tratamento farmacológicoRESUMO
Inhaled liposomal antimicrobials are known to cause hypersensitivity pneumonitis. Amikacin liposome inhalation suspension (ALIS) is a promising novel antimicrobial agent against refractory Mycobacterium avium complex infections. The frequency of drug-induced lung injury caused by ALIS is relatively high. To date, no reports of ALIS-induced organizing pneumonia diagnosed by bronchoscopy are available. We report a case of a 74-year-old female patient presenting with non-tuberculous mycobacterial pulmonary disease (NTM-PD). She was treated with ALIS for refractory NTM-PD. Fifty-nine days after starting ALIS, the patient developed a cough, and her chest radiographs indicated deterioration. She was diagnosed with organizing pneumonia based on pathological findings of the lung tissues obtained by bronchoscopy. After switching from ALIS to amikacin infusion, her organizing pneumonia improved. It is difficult to distinguish between organizing pneumonia and an exacerbation of NTM-PD based on chest radiography alone. Therefore, it is essential to perform an active bronchoscopy for diagnosis.