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1.
Clin Lab ; 70(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38213218

RESUMEN

BACKGROUND: Herpesvirus IgG antibody positivity can be a lifelong burden of disease replication and reinfection or recent viruses can be reactivated and play an important role in the diagnosis and monitoring of herpesvirus [1]. However, sometimes serum IgG antibody positivity is of limited help in determining the onset of disease. We reported a case of herpesvirus IgG antibody positive in a patient with lung cancer who was initially misdiagnosed as herpes simplex and later confirmed drug-induced pemphigus (DIP) by histological and immunofluorescence studies. METHODS: Appropriate laboratory tests, enzyme-linked immunosorbent assay (ELISA), immunofluorescence and histological tests were performed for diagnosis. RESULTS: In lung cancer patients who were positive for herpesvirus IgG antibodies, were initially misdiagnosed as herpes simplex and eventually confirmed by histological and immunofluorescence examinations as DIP. CONCLUSIONS: Positive herpesvirus IgG antibody is not a specific manifestation of herpesvirus infection. For patients with unexplained skin blisters, we should improve histological examinations as soon as possible to clarify the type of lesion.


Asunto(s)
Herpes Simple , Neoplasias Pulmonares , Pénfigo , Humanos , Inmunoglobulina G , Neoplasias Pulmonares/tratamiento farmacológico , Técnica del Anticuerpo Fluorescente , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática
2.
Clin Lab ; 70(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38747927

RESUMEN

BACKGROUND: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer. METHODS: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP. RESULTS: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis. CONCLUSIONS: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.


Asunto(s)
Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico por imagen , Diagnóstico Diferencial , Neumonía en Organización Criptogénica/diagnóstico , Neumonía en Organización Criptogénica/patología , Neumonía en Organización Criptogénica/diagnóstico por imagen , Biopsia , Masculino , Anciano , Persona de Mediana Edad , Pulmón/patología , Pulmón/diagnóstico por imagen , Broncoscopía , Neumonía Organizada
3.
Clin Lab ; 70(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38213214

RESUMEN

BACKGROUND: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease. METHODS: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease. RESULTS: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy. CONCLUSIONS: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.


Asunto(s)
Empiema Tuberculoso , Derrame Pleural , Tuberculosis Pleural , Humanos , Empiema Tuberculoso/diagnóstico , Empiema Tuberculoso/complicaciones , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/patología , Derrame Pleural/etiología , Pleura/patología , Biopsia , Adenosina Desaminasa
4.
Clin Lab ; 70(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38345979

RESUMEN

BACKGROUND: Carcinoembryonic antigen (CEA) is a polysaccharide complex that is found in the human respiratory system. It is of significant use in disease surveillance of lung cancer; however, serum CEA can occasionally only offer little assistance. We present a case of recurring infection initially diagnosed as carcinoembryonic antigen-negative in a patient with a history of hypersensitivity pneumonitis infection, which finally led to the diagnosis of lung adenocarcinoma following percutaneous lung puncture. METHODS: Appropriate laboratory tests, chest CT, bronchoscopy, percutaneous lung puncture, and pathologic examination were performed to explore the cause of the disease. RESULTS: Because CEA was negative and a chest CT showed interstitial changes in both lungs with numerous hyperdense shadows, coupled with the patient's history of hypersensitivity pneumonitis, we initially believed that the infection was relapsing. However, a percutaneous lung puncture eventually revealed that the patient had lung adenocarcinoma. CONCLUSIONS: Vigilance needs to be increased in clinical work for patients with interstitial lung disease, low tumor markers such as CEA, and imaging suggestive of inflammatory progression, which in fact turns into lung cancer. When the treatment is ineffective after standardized application of hormone and anti-infection, lung tissue should be obtained for pathological examination in time to obtain pathological evidence.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Alveolitis Alérgica Extrínseca , Neoplasias Pulmonares , Humanos , Antígeno Carcinoembrionario , Recurrencia Local de Neoplasia , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/patología , Biomarcadores de Tumor , Biopsia
5.
Clin Lab ; 70(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38868891

RESUMEN

BACKGROUND: Non-tuberculous mycobacterial pulmonary infections (NTM-PD) are becoming increasingly common in clinical practice, and early detection and accurate determination of the infecting pathogen is crucial for subsequent treatment. We report a case of NTM-PD in a healthy middle-aged female with Mycobacterium tuberculosis complex group (MAC) infection confirmed by mNGS examination. METHODS: Appropriate laboratory tests, chest CT scan, bronchoscopic alveolar lavage fluid (BALF) examination, and macrogenomic next-generation sequencing (mNGS) were performed to establish the diagnosis. RESULTS: Chest CT showed multiple inflammatory lesions in the right middle lobe, and BALF sent for mNGS finally confirmed the diagnosis of MAC infection. After symptomatic treatment with azithromycin combined with ethambutol and rifampicin, the patient improved and was discharged from the hospital. CONCLUSIONS: In patients with pulmonary infections, pathogens should be clarified early to determine the diagnosis. mNGS of BALF samples have high specificity in detecting pathogens of infectious diseases, especially complex mixed infectious disease pathogens.


Asunto(s)
Líquido del Lavado Bronquioalveolar , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare , Humanos , Femenino , Infección por Mycobacterium avium-intracellulare/diagnóstico , Infección por Mycobacterium avium-intracellulare/microbiología , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infección por Mycobacterium avium-intracellulare/complicaciones , Complejo Mycobacterium avium/aislamiento & purificación , Complejo Mycobacterium avium/genética , Líquido del Lavado Bronquioalveolar/microbiología , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Secuenciación de Nucleótidos de Alto Rendimiento , Neumonía/microbiología , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Azitromicina/uso terapéutico , Rifampin/uso terapéutico
6.
Clin Lab ; 70(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38469771

RESUMEN

BACKGROUND: Pulmonary tuberculosis (PTB) is an important infectious disease that threatens the health and life of human beings. In the diagnosis of PTB, imaging plays a dominant role, but due to the increasing drug resistance of Mycobacterium tuberculosis, atypical clinical manifestations, "different images with the same disease" or "different diseases with the same image" in chest imaging, and the low positivity rate of routine sputum bacteriology, which leads to a high rate of misdiagnosis of PTB. We report a case of pulmonary tuberculosis that was misdiagnosed on imaging. We report a case of pulmonary tuberculosis that resembled sarcoidosis on imaging and was negative for antacid staining on sputum smear and alveolar lavage fluid, and was later diagnosed by microbial next-generation sequencing (NGS). The case was initially misdiagnosed as sarcoidosis. METHODS: Alveolar lavage fluid NGS, chest CT, bronchoscopy. RESULTS: Chest CT showed multiple inflammatory lesions in both lungs, multiple nodular foci in both lungs, and multiple enlarged lymph nodes in the mediastinum and hilar region on both sides. Fiberoptic bronchoscopy was performed in the basal segment of the left lower lobe of the lungs to carry out bronchoalveolar lavage, and the lavage fluid was sent to the NGS test and returned the following results: Mycobacterium tuberculosis complex group detected in the number of sequences of 293. Based on the results of the NGS test, the diagnosis of pulmonary tuberculosis could be confirmed. CONCLUSIONS: The diagnosis of pulmonary tuberculosis cannot be easily excluded in patients with "different images with the same disease" or "different diseases with the same image" on chest imaging without the support of sputum positivity. The goal was to improve the alertness of medical personnel to the misdiagnosis of tuberculosis and the application of NGS technology.


Asunto(s)
Mycobacterium tuberculosis , Sarcoidosis , Tuberculosis Pulmonar , Humanos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Mycobacterium tuberculosis/genética , Líquido del Lavado Bronquioalveolar/microbiología , Sarcoidosis/diagnóstico , Esputo/microbiología , Errores Diagnósticos , Secuenciación de Nucleótidos de Alto Rendimiento , Sensibilidad y Especificidad
7.
J Chem Phys ; 159(8)2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37606334

RESUMEN

A hybrid stochastic simulation method is developed to study H2-O2 auto-ignition at the microscale. Simulation results show that the discrete and stochastic characteristics of reaction collisions have notable impacts on the ignition process, particularly in the early stages when only a few radicals exist. The statistical properties of ignition delay time, which reflect the accumulated stochasticity during ignition, are obtained and analyzed for different initial temperatures and total molecular numbers. It is found that the average and standard deviation of ignition delay time increase as the total molecular number decreases, with this phenomenon being particularly pronounced near the crossover temperature. When the total molecular number is sufficiently small, the chain initiation reaction becomes crucial to the stochastic properties, as its average firing time exhibits an inverse proportionality to the total molecular number. As the total molecular number increases, the influence of other chain reactions intensifies, causing the power law relation between standard deviation and total molecular number to shift from -1 power to -0.5 power. Owing to different chain reaction paths for high- and low-temperature auto-ignition, the strongest relative fluctuation occurs near the crossover temperature. A theoretical equation for the standard deviation of ignition delay time is obtained based on dimensional analysis, giving excellent agreement with the simulation results in both high- and low-temperature modes.

8.
Clin Lab ; 69(2)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36787556

RESUMEN

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause of hospitalization, characterized by high mortality, morbidity, and cost and has serious human health implications. Various scoring criteria have been used to predict the severity of pneumonia, including the CURB-65 score, Pneumonia Severity Index (PSI) score, and Severe Community-Acquired Pneumonia (SCAP) score. However, these scoring criteria have shortcomings such as low sensitivity, cumbersome clinical application, and limited application. This study aimed to construct a nomogram model to predict the severity of CAP patients by blood indicators. METHODS: This is a retrospective study. Patients with CAP were enrolled and then tested by routine blood, coagulation series, biochemical and inflammatory indicators, and general information such as imaging findings and disease history of the patients were recorded. The main observation was the progression of the patients' disease. Univariate analysis and binary logistic regression analysis were used to explore the independent risk factors for the severity of CAP patients, followed by plotting a nomogram to obtain the prediction model and constructing calibration curves to assess the authenticity and accuracy of the prediction model. Finally, the sensitivity, specificity, and other evaluation indexes were calculated by the receiver operating characteristic curve (ROC) to evaluate the clinical application value of the nomogram prediction model. RESULTS: Univariate analysis and binary logistic regression analysis of 277 hospitalized patients yielded platelet to lymphocyte ratio (PLR) and serum amyloid A (SAA) as independent risk factors for the severity of CAP patients. The AUC of the nomogram model for PLR and SAA was 0.889 (95% CI 0.845 - 0.932). The sensitivity was 77.3%, and the specificity was 85.3%, which had an excellent predictive value. CONCLUSIONS: The nomogram model based on PLR and SAA to predict the severity of CAP patients has a high specificity and sensitivity.


Asunto(s)
Infecciones Comunitarias Adquiridas , Neumonía , Humanos , Nomogramas , Pronóstico , Estudios Retrospectivos , Linfocitos , Índice de Severidad de la Enfermedad
9.
Clin Lab ; 69(4)2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37057934

RESUMEN

BACKGROUND: Pulmonary tuberculosis presenting as solitary pulmonary nodules in imaging is sometimes difficult to differentiate from lung cancer and is more likely to be misdiagnosed when accompanied by elevated CEA and positive PET-CT findings. METHODS: By reporting a case of misdiagnosed lung cancer, which was confirmed to be pulmonary tuberculosis by lung biopsy, a joint literature analysis was performed to raise clinicians' awareness of isolated nodules in the lung. RESULTS: With a series of ancillary tests, we initially considered the nodule to be malignant, and the lung biopsy pathology eventually confirmed pulmonary tuberculosis. CONCLUSIONS: When chest imaging suggests the presence of malignant features in solitary pulmonary nodules, invasive procedures can be performed appropriately to clarify the nature of the lesion. The diagnosis cannot be made blindly to ensure that no incorrect diagnosis is made nor wrong treatment given.


Asunto(s)
Neoplasias Pulmonares , Nódulo Pulmonar Solitario , Tuberculosis Pulmonar , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Nódulo Pulmonar Solitario/diagnóstico , Nódulo Pulmonar Solitario/patología , Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tuberculosis Pulmonar/diagnóstico por imagen
10.
Clin Lab ; 69(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37145075

RESUMEN

BACKGROUND: Infectious pulmonary diseases caused by nontuberculous mycobacteria (NTM) are becoming more common in clinical work, and early detection of the bacterium and its early identification are prerequisites for accurate treatment. METHODS: By reporting a case of confirmed NTM infection in a patient with connective tissue disease-associated interstitial lung fibrosis, a joint literature analysis was performed to improve clinicians' understanding of NTM and the clinical application of targeted next-generation sequencing (tNGS). RESULTS: Chest CT suggested a partially enlarged cavitary lesion in the upper lobe of the right lung, combined with positive sputum antacid staining, and sputum tNGS was sent to confirm the final diagnosis of Mycobacterium paraintracellulare infection. CONCLUSIONS: The successful application of tNGS helps in the rapid diagnosis of NTM infection. It also reminds medical practitioners to consider the presence of NTM infection in advance in the presence of many NTM infection factors, combined with imaging manifestations.


Asunto(s)
Enfermedades del Tejido Conjuntivo , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium , Humanos , Infecciones por Mycobacterium no Tuberculosas/complicaciones , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Micobacterias no Tuberculosas , Fibrosis
11.
Clin Lab ; 69(9)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37702676

RESUMEN

BACKGROUND: Current studies have reported that it is rare for the coronavirus disease 2019 (COVID-19) to be combined with two fungal infections and that COVID-19 can be combined with multiple cardiovascular complications, both of which can complicate the condition and increase the risk of death. METHODS: We report a case of COVID-19 in which Aspergillus fumigatus and Cryptococcus neoformans were detected by sputum targeted next-generation sequencing (tNGS) and cardiac monitoring during treatment revealed cardiovascular complications. RESULTS: We consider that this patient's fungal infection was associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the application of corticosteroids. In addition, cardiovascular complications were associated with an inflammatory response and increased sympathetic stimulation due to SARS-CoV-2 infection. CONCLUSIONS: The presence of COVID-19-associated fungal infections cannot be excluded when multiple risk factors for fungal infections are present in patients with COVID-19 and the condition is rapidly deteriorating. Effective long-term monitoring of cardiac function during the patient's hospitalization is necessary to reduce morbidity and mortality.


Asunto(s)
COVID-19 , Criptococosis , Insuficiencia Cardíaca , Humanos , COVID-19/complicaciones , Aspergillus fumigatus , SARS-CoV-2 , Insuficiencia Cardíaca/diagnóstico
12.
Clin Lab ; 69(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948488

RESUMEN

BACKGROUND: Detection of serum neuron specific enolase (NSE) has high sensitivity and specificity in the diagnosis of lung cancer, especially small cell lung cancer, but sometimes serum NSE provides limited help. We report a case of high-density shadow of the left lung and elevated serum NSE which mimicked lung cancer. It was ultimately confirmed to be pulmonary aspergillosis (PA) by bronchoscopic alveolar lavage fluid (BALF) and next-generation sequencing (NGS). METHODS: Appropriate laboratory tests, chest computed tomography (CT) scan, bronchoscopic alveolar lavage fluid, and next-generation sequencing were used to explore latent causes. RESULTS: NSE level was elevated, chest CT scan showed high-density shadow of the left lung, bronchoscopy showed flesh-colored new organisms in the lower lobe of the left lung, BALF and NGS revealed the presence of Aspergillus. CONCLUSIONS: Elevated NSE is not a typical manifestation of lung cancer, and we should perform BALF and NGS early to determine whether there is infection with special pathogenic bacteria.


Asunto(s)
Enfermedades Pulmonares , Neoplasias Pulmonares , Aspergilosis Pulmonar , Humanos , Pulmón/patología , Neoplasias Pulmonares/patología , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/patología , Fosfopiruvato Hidratasa
13.
Clin Lab ; 69(11)2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37948490

RESUMEN

BACKGROUND: Carcinoembryonic antigen (CEA) is a polysaccharide complex present in the human respiratory system, which can reflect the presence of tumors in the human body and has important value in the monitoring of lung cancer [1], but sometimes serum CEA provides limited help. We reported a case of multiple consolidation of the lungs with elevated serum CEA, initially misdiagnosed as lung cancer and eventually confirmed by bronchoscopic lung biopsy as pulmonary cryptococcosis (PC). METHODS: Appropriate laboratory examination, chest computed tomography (CT) scan, and bronchoscopy lung biopsy were used to explore the latent etiology. RESULTS: CEA level was elevated, chest CT scan showed multiple consolidation of the lungs, serum cryptococcal antigen was positive, and pathological findings on bronchoscopic lung biopsy confirmed pulmonary cryptococcosis. CONCLUSIONS: Elevated CEA is not typical of lung cancer. We should also consider the possibility of specific pathogenic infection. Bronchoscopic lung biopsy is the gold standard should be performed as soon as possible to identify the lesion.


Asunto(s)
Criptococosis , Enfermedades Pulmonares , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Antígeno Carcinoembrionario , Pulmón/diagnóstico por imagen , Pulmón/patología , Criptococosis/diagnóstico , Errores Diagnósticos
14.
Clin Lab ; 69(10)2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37844045

RESUMEN

BACKGROUND: Acute Eosinophilic Pneumonia (AEP) is a rare form of non-infectious pneumonia that is easily missed and misdiagnosed because of its atypical clinical symptoms and misleading laboratory and imaging studies. METHODS: By reporting a case of an initial diagnosis of lung abscess, which was treated with antibiotics and then CT suggesting that the lesion continued to worsen, it was eventually confirmed to be AEP by lung biopsy, A joint literature analysis was conducted to improve clinicians' understanding of the diagnosis and treatment of AEP. RESULTS: Initially, because of the atypical ancillary findings, we thought the disease was a lung abscess, which was eventually confirmed by pathology as AEP. CONCLUSIONS: The presence of AEP needs to be considered when various laboratory findings point to infectious dis-ease, but anti-infection is not effective. Diagnosis can be confirmed by bronchoalveolar lavage and lung tissue biopsy. Prompt treatment can provide rapid relief and reduce the risk of patient death.


Asunto(s)
Absceso Pulmonar , Eosinofilia Pulmonar , Humanos , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/patología , Absceso Pulmonar/diagnóstico , Absceso Pulmonar/complicaciones , Enfermedad Aguda , Pulmón/diagnóstico por imagen , Pulmón/patología , Líquido del Lavado Bronquioalveolar
15.
Clin Lab ; 69(4)2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37057935

RESUMEN

BACKGROUND: Organizing pneumonia (OP) is a pathologic concept characterized by the formation of granulation tissue from fibroblasts, myofibroblasts, collagen, and fibrotic exudate in the respiratory fine bronchi, alveolar ducts, and alveoli. The clinical imaging of mechanized pneumonia is variable, and histopathological examination is required to clarify the nature of the lesion when imaging is atypical. We report a case of OP with imaging resem-blance to pulmonary tuberculosis and false-positive next-generation sequencing (NGS), which was first misdiag-nosed as pulmonary tuberculosis. METHODS: Appropriate laboratory tests, alveolar lavage fluid NGS, chest CT, bronchoscopy, percutaneous lung puncture, pathology. RESULTS: Chest CT showed a nodular high-density shadow in the lower lobe of the right lung. According to the chest CT, bronchoalveolar lavage was performed in the dorsal segment of the right lower lobe of the lung. NGS of lavage fluid: the sequence number of Moraxella osseae was 1,423; the sequence number of Prevotella melanogaster was 1,129. Based on lung histopathology, fibrous emboli and necrotic material were seen in the alveolar lumen, and the final diagnosis of the OP was confirmed. CONCLUSIONS: It should be noted that physicians should not blindly believe the NGS result report. When the diagnosis is not clear and anti-infection treatment is ineffective, lung tissue should be obtained promptly for pathological examination to obtain pathological evidence to differentiate from misdiagnosed diseases.


Asunto(s)
Neumonía Organizada , Neumonía , Tuberculosis Pulmonar , Tuberculosis , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neumonía/diagnóstico por imagen , Tuberculosis/diagnóstico , Fibrosis , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/patología , Secuenciación de Nucleótidos de Alto Rendimiento
16.
J Virol ; 95(22): e0147121, 2021 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-34468172

RESUMEN

Human norovirus is the leading cause of gastroenteritis worldwide, with no approved vaccine or antiviral treatment to mitigate infection. These plus-strand RNA viruses have T = 3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers, to which antibodies and cellular receptors bind. We previously demonstrated that bile binding to the capsid of mouse norovirus (MNV) causes several major conformational changes; the entire P domain rotates by ∼90° and contracts onto the shell, the P domain dimers rotate about each other, and the structural equilibrium of the epitopes at the top of the P domain shifts toward the closed conformation, which favors receptor binding while blocking antibody binding. Here, we demonstrate that MNV undergoes reversible conformational changes at pH 5.0 that are nearly identical to those observed when bile binds. Notably, at low pH or when metals bind, a cluster of acidic resides in the G'-H' loop interact and distort the G'-H' loop, and this may drive C'-D' loop movement toward the closed conformation. Enzyme-linked immunosorbent assays with infectious virus particles at low pH or in the presence of metals demonstrated that all tested antibodies do not bind to this contracted form, akin to what was observed with the MNV-bile complex. Therefore, low pH, cationic metals, and bile salts are physiological triggers in the gut for P domain contraction and structural rearrangement, which synergistically prime the virus for receptor binding while blocking antibody binding. IMPORTANCE The protruding domains on the calicivirus capsids are recognized by cell receptors and antibodies. We demonstrated that MNV P domains are highly mobile, and bile causes contraction onto the shell surface while allosterically blocking antibody binding. We present the near-atomic cryo-electron microscopy structures of infectious MNV at pH 5.0 and pH 7.5. Surprisingly, low pH is sufficient to cause the same conformational changes as when bile binds. A cluster of acidic residues on the G'-H' loop were most likely involved in the pH effects. These residues also bound divalent cations and had the same conformation as observed here at pH 5. Binding assays demonstrated that low pH and metals block antibody binding, and thus the G'-H' loop might be driving the conformational changes. Therefore, low pH, cationic metals, and bile salts in the gut synergistically prime the virus for receptor binding while blocking antibody binding.


Asunto(s)
Anticuerpos Antivirales/metabolismo , Infecciones por Caliciviridae/virología , Proteínas de la Cápside/metabolismo , Norovirus/metabolismo , Virión/metabolismo , Humanos , Unión Proteica , Conformación Proteica , Dominios Proteicos
17.
J Virol ; 95(13): e0017621, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-33827952

RESUMEN

Noroviruses, members of the Caliciviridae family, are the major cause of epidemic gastroenteritis in humans, causing ∼20 million cases annually. These plus-strand RNA viruses have T=3 icosahedral protein capsids with 90 pronounced protruding (P) domain dimers to which antibodies and cellular receptors bind. In the case of mouse norovirus (MNV), bile salts have been shown to enhance receptor (CD300lf) binding to the P domain. We demonstrated previously that the P domains of several genotypes are markedly flexible and "float" over the shell, but the role of this flexibility was unclear. Recently, we demonstrated that bile causes a 90° rotation and collapse of the P domain onto the shell surface. Since bile binds distally to the P-shell interface, it was not at all clear how it could cause such dramatic changes. Here, we present the near-atomic resolution cryo-electron microscopy (cryo-EM) structure of the MNV protruding domain complexed with a neutralizing Fab. On the basis of previous results, we show here that bile salts cause allosteric conformational changes in the P domain that block antibody recognition of the top of the P domain. In addition, bile causes a major rearrangement of the P domain dimers that is likely responsible for the bile-induced collapse of the P domain onto the shell. In the contracted shell conformation, antibodies to the P1 and shell domains are not expected to bind. Therefore, at the site of infection in the gut, the host's own bile allows the virus to escape antibody-mediated neutralization while enhancing cell attachment. IMPORTANCE The major feature of calicivirus capsids is the 90 protruding domains (P domains) that are the site of cell receptor attachment and antibody epitopes. We demonstrated previously that these P domains are highly mobile and that bile causes these "floating" P domains in mouse norovirus (MNV) to contract onto the shell surface. Here, we present the near-atomic cryo-EM structure of the isolated MNV P domain complexed with a neutralizing Fab fragment. Our data show that bile causes two sets of changes. First, bile causes allosteric conformational changes in the epitopes at the top of the P domain that block antibody binding. Second, bile causes the P domain dimer subunits to rotate relative to each other, causing a contraction of the P domain that buries epitopes at the base of the P and shell domains. Taken together, the results show that MNV uses the host's own metabolites to enhance cell receptor binding while simultaneously blocking antibody recognition.


Asunto(s)
Anticuerpos Antivirales/inmunología , Ácidos y Sales Biliares/metabolismo , Evasión Inmune/inmunología , Norovirus/inmunología , Receptores Virales/metabolismo , Animales , Cápside/inmunología , Proteínas de la Cápside/metabolismo , Microscopía por Crioelectrón , Hibridomas , Ratones , Unión Proteica/fisiología , Dominios Proteicos/inmunología
18.
Clin Lab ; 68(12)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36546747

RESUMEN

BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) causes fewer infections, and it causes invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS) that can lead to a poor prognosis for patients. METHODS: Next-generation sequencing (NGS), sputum culture, drug sensitivity test, and other examination methods can detect the specific situation of pathogens in advance. RESULTS: The patient was determined to have CR-hvKP infection after NGS, sputum culture, and drug sensitivity test, and improved after treatment. CONCLUSIONS: When antibiotics are applied in the presence of infection but symptoms do not improve, relevant laboratory or other tests should be performed promptly, and the selection of appropriate antibiotics may improve the survival rate of patients.


Asunto(s)
Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Absceso Hepático , Humanos , Klebsiella pneumoniae/genética , Virulencia , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Absceso Hepático/diagnóstico , Absceso Hepático/tratamiento farmacológico , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico
19.
Zhonghua Wai Ke Za Zhi ; 60(1): 90-94, 2022 Jan 01.
Artículo en Zh | MEDLINE | ID: mdl-34954953

RESUMEN

Objective: To examine the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage Ⅲ tuberculous empyema. Methods: From August 2017 to July 2020, 158 patients of stage Ⅲ tuberculous empyema underwent uniportal VATS decortication with partial rib resection and customized periosteal stripper in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. There were 127 males and 31 females, aged (M(IQR)) 32(28) years (range:14 to 78 years). Follow-up was performed in the outpatient clinic or via social communication applications, at monthly thereafter. If there was no air leak and chest tube drainage was less than 50 ml/day, a chest CT was performed. If the lung was fully re-expanded, chest tubes were removed. All patients received a follow-up chest CT 3 to 6 months following their initial operations which was compared to their preoperative imaging. Results: There was one conversion to open thoracotomy. The operative time was 2.75 (2.50) hours (range: 1.5 to 7.0 hours), and median blood loss was 100 (500) ml (range: 50 to 2 000 ml). There were no perioperative mortalities. There were no major complications except 1 case of redo-VATS for hemostasis due to excessive drainage and 1 case of incision infection, The incidence of prolonged air leaks (>5 days) was 80.3%(126/157). The postoperative hospital stay was 5.00 (2.25) days (range: 2 to 15 days). All patients were discharged with 2 chest tubes, and the median duration drainage was 21.00 (22.50) days (range: 3 to 77 days). Follow-up was completed in all patients over a duration of 20 (14) months (range: 12 to 44 months). At follow-up, 149 patients(94.9%) recovered to grade Ⅰ level, 7 patients to grade Ⅱ level, and 1 patient to grade Ⅲ level. Conclusion: Uniportal VATS decortication involving partial rib resection and a customized periosteal stripper is safe and effective for patients with stage Ⅲ tuberculous empyema.


Asunto(s)
Empiema Tuberculoso , Anciano , China , Empiema Tuberculoso/cirugía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Cirugía Torácica Asistida por Video , Toracotomía
20.
Ann Oncol ; 32(9): 1148-1156, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34116144

RESUMEN

BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. CONCLUSIONS: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.


Asunto(s)
Inmunoconjugados , Neoplasias de la Mama Triple Negativas , Anticuerpos Monoclonales Humanizados , Biomarcadores , Camptotecina/análogos & derivados , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética
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