Urinary Antigen Research Articles

Evaluation of a Rapid Urine Antigen Detection Assay as a Point-of-Care Test in the Diagnosis of Community-Acquired Pneumonia.

Introduction Community-acquired pneumonia (CAP) is among the most common public health problems encountered throughout the world. CAP is a frequent cause of lower respiratory tract infections among children and geriatric-age persons. The etiology of CAP is complex but generally involves infection with bacteria likeStreptococcus pneumoniae (S. pneumoniae), which is the most common cause of CAP. The underdiagnosis of CAP due to the limitations of conventional culture methods could be responsible for severe morbidity and mortality, especially among susceptible populations.We evaluated the usefulness of a rapid immunochromatographic test (BinaxNOW™, Abbott, Chicago, IL) that detects S. pneumoniae through a rapid urine antigen test (RUAT) as a point-of-care (POC) diagnostic method in the early detection of CAP. Methods A prospective study was conducted in a university-affiliated teaching hospital between January 2019 and September 2019 (nine months). The study recruited 300 inpatients who revealed signs and symptoms associated with pneumonia. The study was approved by the institutional ethics committee, and all participants provided their voluntary informed consent.Laboratory evaluationincluded the collection of sputum samples, which were processed for Gram stain and routine culture. Five milliliters of blood were collected from all the subjects for carrying out a blood culture. A urine sample was collected from each participant for the detection of S. pneumoniae through the point-of-care urinary antigen test. Results Of the 300 patients diagnosed with CAP, the S. pneumoniae RUAT was positive in 110 out of 140 cases of pneumococcal pneumoniae (78.57%). The RUAT results were positive for 20 (66.6%) out of 30 bacteremic patients and for 90 (81.8%) out of 110 patients positive for sputum culture. The RUAT was positive in 10 out of 20 cases of pneumonia with an unknown microbial etiology. The overall sensitivity (78.57%), specificity (100%), positive predictive value (100%), negative predictive value (98.88%), and accuracy (90%) of the RUAT were similar to sputum culture results. Conclusion The RUAT has shown comparable efficacy with sputum culture and therefore can be used as a complementary approach to conventional methods in the early diagnosis of CAP caused byS. pneumoniae.Due toits ease of use andrapid results, it could be incorporated as a POC diagnostic test.

The Impact of Viral and Bacterial Co-Infections and Home Antibiotic Treatment in SARS-CoV-2 Hospitalized Patients at the Policlinico Tor Vergata Hospital, Rome, Italy.

Co-infections during COVID-19 may worsen patients' outcomes. This study reports the results of a screening assessing the presence of co-infections among patients hospitalized for SARS-CoV-2 infection in the Infectious Diseases-Ward of the Policlinico Tor Vergata Hospital, Rome, Italy, from 1 January to 31 December 2021. Data on hepatitis B and C virus, urinary antigens for legionella pneumophila and streptococcus pneumoniae, pharyngeal swab for respiratory viruses, QuantiFERON®-TB Gold Plus assay (QFT-P), blood cultures and pre-hospitalization antibiotic prescription were recorded. A total of 482 patients were included, 61% males, median age of 65 years (IQR 52-77), median Charlson comorbidity index of 4 (IQR 2-5). The mortality rate was 12.4%; 366 patients needed oxygen supply. In total, 151 patients (31.3%) received home antibiotics without any association with the outcome. No significant association between mortality and the positivity of viral hepatitis markers was found. Out of 442 patients, 125 had an indeterminate QFT-P, associated with increased mortality. SARS-CoV-2 was the only respiratory virus detected among 389 pharyngeal swabs; 15/428 patients were positive for S. pneumoniae; none for L. pneumophila. In total, 237 blood cultures were drawn within 48 h from hospital admission: 28 were positive and associated with increased mortality. In our cohort, bacterial and viral co-infections in COVID-19 hospitalized patients were rare and not associated with higher mortality.

Trends of legionellosis reported in Jeju Province, Republic of Korea, 2015-2022.

The number of reported cases of Legionnaires' disease (LD) in the Republic of Korea surged nationally in 2016; however, in 2022, this number was higher in Jeju Province than the previous national peak. A descriptive epidemiological study was conducted to analyze trends in the incidence of reported LD cases in Jeju Island from 2015 to 2022. The data for this study were obtained from case reports submitted to the Korea Disease Control and Prevention Agency through its Disease and Health Integrated Management System. The selection criteria were cases or suspected cases of LD reported among Jeju residents between 2015 and 2022. The 95% confidence interval of the crude incidence rate was calculated using the Poisson distribution. Since 2020, the incidence rate of LD in Jeju has risen sharply, showing a statistically significant difference from the national incidence rate. A particular medical institution in Jeju reported a significant number of LD cases. Screening with the urine antigen test (UAT) also increased significantly. Our findings indicate that the rapid increase in cases of LD in Jeju Province since 2020 was due to the characteristics of medical-care use among Jeju residents, which were focused on a specific medical institution. According to their clinical practice guidelines, this medical institution conducted UATs to screen patients suspected of pneumonia.

Evaluation of the Histoplasma capsulatum 100-kilodalton antigen dot blot for the rapid diagnosis of progressive histoplasmosis in HIV/AIDS patients

Among people living with HIV (PLHIV), progressive disseminated histoplasmosis (PDH) represents an important cause of mortality. Since antigen detection allows a rapid diagnosis and the instauration of a specific treatment this study aimed to evaluate the analytical performance of the Hcp100 dot blot, an in-house assay that detects the Histoplasma capsulatum 100-kilodalton antigen in urine and compare it with 2 commercially available assays the Histoplasma Urine Antigen Lateral Flow Assay (MVD-LFA) (MiraVista® Diagnostics) and the Clarus Histoplasma Galactomannan EIA (Clarus HGM) (IMMY). Urine specimens from 23 PLHIV with PDH, 13 patients with other infectious diseases, and 20 healthy individuals were tested. The Hcp100 dot blot showed higher sensitivity (87.0%), specificity (97.0%) and accuracy (92.9%) than the MVD-LFA (73.9%, 78.8%, and 76.8%, respectively) and the Clarus HGM (78.3%, 90.9%, and 85.7%, respectively). The Hcp100 dot blot had high analytical performance and would be a valuable screening tool for diagnosing PDH among PLHIV.

The serotype-specific prevalence of pneumococci in hospitalized pneumonia patients with COPD: a prospective, multi-center, cohort study.

The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Measurement of urinary exosomal phospholipase A2 receptor is a sensitive method for diagnosis of PLA2R-associated membranous nephropathy.

The discovery of phospholipase A2 receptor (PLA2R) and its antibody (aPLA2Rab) has paved the way for diagnosing PLA2R-associated membranous nephropathy (PLA2R-MN) with a high specificity of 98%. However, the sensitivity was only 40% to 83.9%, and there is ongoing discussion around determining the optimal threshold for diagnosis. Recent advancements in the use of exosomes, a novel form of "liquid biopsy," have shown great promise in identifying markers for various medical conditions. Protein mass spectrometry and western blot were applied to verify the existence of PLA2R antigen in the urine exosome. We then evaluated the efficacy of urinary exosomal PLA2R antigen alone or combined with serum aPLA2Rab level to diagnose PLA2R-MN. The urinary exosomes contained a high abundance of PLA2R antigen as evidenced by protein mass spectrometry and western blot in 85 PLA2R-MN patients vs the disease controls (14 secondary MN patients, 22 non-MN patients and 4 PLA2R-negative MN patients) and 20 healthy controls. Of note, urinary exosomal PLA2R antigen abundance also had a good consistency with the PLA2R antigen level in the renal specimens of PLA2R-MN patients. The sensitivity of urinary exosomal PLA2R for diagnosing PLA2R-MN reached 95.4%, whereas the specificity was 63.3%. Combining detection of the urinary exosomal PLA2R and serum aPLA2Rab could develop a more sensitive diagnostic method for PLA2R-MN, especially for patients with serum aPLA2Rab ranging from 2 to 20 RU/mL. Measurement of urinary exosomal PLA2R could be a sensitive method for the diagnosis of PLA2R-MN.

Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort

ObjectivesThe objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH.MethodsSeventy-three (n = 73) PLWH (median CD4 3–6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test.ResultsAlthough the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally.ConclusionsOur study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations.

Comparison of a Urine Antigen Assay and Multiple Examinations with the Formalin-Ethyl Acetate Concentration Technique for Diagnosis of Opisthorchiasis.

Detection of worm antigen in urine is a sensitive diagnostic method for opisthorchiasis, particularly for light-intensity infections; however, the presence of eggs in feces is essential for validating results from the antigen assay. To address the issue of low sensitivity of fecal examination, we modified the protocol for the formalin-ethyl acetate concentration technique (FECT) and compared it against urine antigen measurements for detection of the parasite Opisthorchis viverrini. First, we optimized the FECT protocol by increasing the number of drops for examinations from the standard two drops to a maximum of eight. We were able to detect additional cases after examination of ≥ 3 drops, and the prevalence of O. viverrini saturated after examination of ≥ 5 drops. We then compared the optimized FECT protocol (examining five drops of suspension) against urine antigen detection for the diagnosis of opisthorchiasis in field-collected samples. The optimized FECT protocol detected O. viverrini eggs in 25 of 82 individuals (30.5%) who had positive urine antigen tests but were fecal egg negative by the standard FECT protocol. The optimized protocol also retrieved O. viverrini eggs in 2 of 80 antigen-negative cases (2.5%). In comparison with the composite reference standard (combined FECT and urine antigen detection), the diagnostic sensitivity of examining two and five drops of FECT and the urine assay was 58.2, 67, and 98.8%, respectively. Our results show that multiple examinations of fecal sediment increase the diagnostic sensitivity of FECT and thus provide further support for the reliability and utility of the antigen assay for diagnosis and screening of opisthorchiasis.

Pneumococcal Endocarditis, Rare but Not Forgotten

Pneumococcal endocarditis incidence has significantly decreased since the advent of antibiotics but remains a significant cause of mortality and morbidity in high-risk groups, such as those with heart disease, chronic lung and liver disease, smoking, diabetes mellitus, and immunosuppression. We present a unique case of pneumococcal endocarditis with no clinical stigmata of infective endocarditis that manifested with acute hypoxic respiratory failure and severe aortic regurgitation. A large vegetation on the aortic valve was noted during surgery, with negative blood cultures and aortic valve tissue cultures but positive Streptococcus pneumoniae urinary antigen and polymerase chain reaction (PCR) test on the aortic valve.

Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing

ObjectivesTo analyze the differences in short- and long-term prognosis and the predictors of survival between patients with community-acquired Legionella and Streptococcus pneumoniae pneumonia, diagnosed early by urinary antigen testing (UAT). MethodsProspective multicenter study conducted in immunocompetent patients hospitalized with community-acquired Legionella or pneumococcal pneumonia (L-CAP or P-CAP) between 2002-2020. All cases were diagnosed based on positive UAT. ResultsWe included 1452 patients, 260 with community-acquired Legionella pneumonia (L-CAP) and 1192 with community-acquired pneumococcal pneumonia (P-CAP). The 30-day mortality was higher for L-CAP (6.2%) than for P-CAP (5%). After discharge and during the median follow-up durations of 11.4 and 8.43 years, 32.4% and 47.9% of patients with L-CAP and P-CAP died, and 82.3% and 97.4% died earlier than expected, respectively. The independent risk factors for shorter long-term survival were age >65 years, chronic obstructive pulmonary disease, cardiac arrhythmia, and congestive heart failure in L-CAP and the same first three factors plus nursing home residence, cancer, diabetes mellitus, cerebrovascular disease, altered mental status, blood urea nitrogen ≥30 mg/dl, and congestive heart failure as a cardiac complication during hospitalization in P-CAP. ConclusionIn patients diagnosed early by UAT, the long-term survival after L-CAP or P-CAP was shorter (particularly after P-CAP) than expected, and this shorter survival was mainly associated with age and comorbidities.

Should urine antigen testing forLegionella pneumophilabe ordered for all hospitalized patients with community-acquired pneumonia?

Should urine antigen testing for<i>Legionella pneumophila</i>be ordered for all hospitalized patients with community-acquired pneumonia?

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

An Atypical Presentation of X-linked Lymphoproliferative Disease type 1 Presenting with Seronegative Coccidioidomycosis

X-linked lymphoproliferative disease (XLP-1), an inborn error of immunity (IEI) caused by pathogenic variants in SH2D1A encoding signaling lymphocyte activation molecule-associated protein (SAP), is characterized by hemophagocytic lymphohistiocytosis (HLH), lymphoma, and hypogammaglobulinemia. We report the first known case of XLP-1 presenting with seronegative coccidioidomycosis. CaseA 13-year-old boy with persistent asthma, recurrent otitis media requiring four sets of tympanostomy tubes, chronic sinusitis, and Common Variable Immunodeficiency (CVID) presented with acute-on-chronic hypoxic respiratory failure. He had been off subcutaneous immunoglobulin (SCIg) replacement for 2 years. Sputum culture was positive for H. influenzae, treated with cefepime and azithromycin and supplemental oxygen for acute hypoxic respiratory failure. Fever persisted despite 48 hours of antibiotics. CT chest showed bronchiectasis with mediastinal, subcarinal and hilar adenopathy. Coccidioides immitis IgG and IgM were negative, but urine antigen was positive. There was no radiologic or cerebrospinal fluid evidence of disseminated coccidioidomycosis.Immunologic workup revealed undetectable IgG, IgA, IgM, and IgE (table 1). Lymphocyte subsets showed severe T and NK cell lymphopenia. Total B cell count was normal, but he had decreased CD19+27+ and transitional B cells, with absent switched memory B cells and no plasmablasts (table 1). Lymphocyte proliferation to mitogens/antigens was decreased. Serum ferritin was normal, and EBV PCR was negative. A targeted 429-gene panel identified a hemizygous variant of uncertain significance (VUS) in SH2D1A, c.82_102dup (p.Ser28_Ser34dup). SAP expression was absent in CD4+ T cells and NK cells with a bimodal expression in CD8+ T cells, suggesting possible mosaicism in this subset. He was diagnosed with X-linked lymphoproliferative disease 1 (XLP-1) and treated with fluconazole, trimethoprim-sulfamethoxazole prophylaxis, and IgG replacement (1 g/kg intravenous initially, then transitioned to weekly SCIg targeting an IgG >1000 mg/dL), with clinical improvement, resolution of fevers and acute hypoxia. He was referred for hematopoietic cell transplant evaluation.Coccidioidomycosis has not been described in a new diagnosis of XLP-1 and should be considered in this IEI. Coccidioidomycosis susceptibility has been reported in other IEIs including impaired interleukin-12/interferon-gamma axis signaling, STAT3 loss of function, chronic granulomatous disease, and recently cytidine triphosphate synthase 1 (CTPS1) deficiency.Table 1Patient’s immunologic variables compared to reference range. Absolute values are shownImmunologic VariablePatient ValuesReference RangeIgG<70 (L)<70 mg/dLIgA<15 (L)<15 mg/dLIgM<8 (L)<8 mg/dLIgE<1.5 (L)<1.5 IU/uLTotal CD4+ T Cells11 (L)570–2400 cells/uLTotal CD8+ T Cells63 (L)210–1200 cells/uLTotal CD19+ B cells173165–1154 cells/uLCD19+ CD24++ CD38++ (Transitional B Cells)0 (L)8–392 cells/uLCD19+CD24+CD38+ (Naïve B Cells)12159–1146 cells/uLCD19+CD27-(Naïve B cells)169140–2269 cells/uLCD19+ CD27+ CD38+ IgM- (Plasmablasts)0<30 cells/uLCD19+CD27+IgD-IgM- (Switched-memory B cells)0 (L)6–190 cells/uLCD16+ CD56+ (NK Cells)32 (L)78–470 cells/uLL – low

Evaluation of an enzyme immunoassay and immunodiffusion for detection of anti-Histoplasma antibodies in serum from cats and dogs.

Histoplasma antigen and anti-Histoplasma antibody detection are used to support the diagnosis of histoplasmosis. There is a paucity of published data on antibody assays. Our primary hypothesis was that anti-Histoplasma immunoglobulin G (IgG) antibody detection using enzyme immunoassay (EIA) will be more sensitive as compared to immunodiffusion (ID). Thirty-seven cats and 22 dogs with proven or probable histoplasmosis; 157 negative control animals. Residual stored sera were tested for anti-Histoplasma antibodies using EIA and ID. Results of urine antigen EIA were reviewed retrospectively. Diagnostic sensitivity was calculated for all three assays and compared between immunoglobulin G (IgG) EIA and ID. The diagnostic sensitivity of urine antigen EIA and IgG EIA, interpreted in parallel, was reported. Sensitivity of IgG EIA was 30/37 (81.1%; 95% confidence interval [CI], 68.5%-93.4%) in cats and 17/22 (77.3%; 95% CI, 59.8%-94.8%) in dogs. Diagnostic sensitivity of ID was 0/37 (0%; 95% CI, 0%-9.5%) in cats and 3/22 (13.6%; 95% CI, 0%-28.0%) in dogs. Immunoglobulin G EIA was positive in all animals (2 cats and 2 dogs) with histoplasmosis but without detectable antigen in urine. Diagnostic specificity of IgG EIA was 18/19 (94.7%; 95% CI, 74.0%-99.9%) in cats and 128/138 (92.8%; 95% CI, 87.1%-96.5%) in dogs. Antibody detection by EIA can be used to support the diagnosis of histoplasmosis in cats and dogs. Immunodiffusion has an unacceptably low diagnostic sensitivity and is not recommended.

SARS-CoV-2 N-Antigen Quantification in Respiratory Tract, Plasma and Urine: Kinetics and Association with RT-qPCR Results.

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, we tested 26 patients for viral RNA and N-antigen in respiratory samples, plasma and urine. This allowed us to compare the kinetics between the three compartments and to compare RNA and antigen concentrations in each. Our results showed the presence of N-antigen in respiratory (15/15, 100%), plasma (26/59, 44%) and urine (14/54, 28.9%) samples, whereas RNA was only detected in respiratory (15/15, 100%) and plasma (12/60, 20%) samples. We detected N-antigen in urine and plasma samples until the day 9 and day 13 post-inclusion, respectively. The antigen concentration was found to correlate with RNA levels in respiratory (p < 0.001) and plasma samples (p < 0.001). Finally, urinary antigen levels correlated with plasma levels (p < 0.001). Urine N-antigen detection could be part of the strategy for the late diagnosis and prognostic evaluation of COVID-19, given the ease and painlessness of sampling and the duration of antigen excretion in this biological compartment.

Problemas clínicos en Micología Médica: problema número 56

We present the case of a twenty six year-old woman with rheumatoid arthritis, treated with certolizumab. She sought medical attention due to cough, fever and night sweats. X-ray exam showed a miliary pneumonia. She was treated for tuberculosis and 50days later she presented with aphasia. Magnetic nuclear resonance revealed brain lesions. Histoplasma capsulatum PCR test and urinary antigen were positive, so an antifungal treatment with voriconazole was started. Visual adverse effects forced to change the antifungal schedule in both the length of treatment and the antifungal drug. With this measure the patient progressed favorably. The test of urinary Histoplasma capsulatum antigen and PCR amplification were key to make a diagnosis and also for a follow-up.

MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP40-01 DIFFERENTIALLY EXPRESSED GLYCOPROTEINS IN PRE- AND POST- DIGITAL RECTAL EXAMINATION URINE SAMPLES FOR DETECTING AGGRESSIVE PROSTATE CANCER Indu Kohaar, Yuefan Wang, Tung-Shing Mamie Lih, Naseruddin Höti, Lori Sokoll, Gregory Chesnut, Gyorgy Petrovics, and Hui Zhang Indu KohaarIndu Kohaar More articles by this author , Yuefan WangYuefan Wang More articles by this author , Tung-Shing Mamie LihTung-Shing Mamie Lih More articles by this author , Naseruddin HötiNaseruddin Höti More articles by this author , Lori SokollLori Sokoll More articles by this author , Gregory ChesnutGregory Chesnut More articles by this author , Gyorgy PetrovicsGyorgy Petrovics More articles by this author , and Hui ZhangHui Zhang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) is predominantly indolent disease with a small fraction of patients undergoing metastatic progression. Therefore, it is critical to identify non-invasive diagnostic markers for the early detection of an aggressive PCa subtype. We hypothesized that non-invasive pre-digital rectal examination (pre-DRE) urine specimens harbor molecular signatures of aggressive PCa, which can help in the clinical management of the disease. Previously, we had systematically evaluated urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) using post-DRE urine specimens. The goal of the study is to explore the potential of using pre-DRE urine specimens for detecting AG-CaP and validate the post-DRE findings. METHODS: This is a retrospective case cohort study based on 154 pre-DRE urine specimens collected by the Center for Prostate Disease Research under an institutional review board approved protocol from men undergoing diagnostic biopsy. We performed an optimized quantitative mass spectrometric analysis to evaluate the association of markers with aggressive PCa at diagnosis. The cohort comprised 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score=6), and 65 patients with AG-PCa (Gleason score 7 or above). Targeted analyses of AG-PCa-associated glycoproteins previously identified in post-DRE urine samples were also applied to validate the post-DRE findings in non-DRE specimens. Data-independent acquisition mass spectrometry (DIA-MS) analysis was performed for glycosite-containing peptides. Fisher exact and Wilcoxon-Mann-Whitney tests were used for categorical and continuous variables respectively and logistic regression was evaluated using receiver operating characteristic (ROC) analysis for the urinary markers and marker panels. RESULTS: Urinary prostatic acid phosphatase (ACPP), CD97 antigen (CD97), and prostate-specific antigen (PSA) levels in pre-DRE specimens were associated with patients with AG-PCa compared to cancer-negative and non-AG-PCa. The analysis confirmed three of the previously reported post-DRE urinary glycoproteins and identified three new AG-PCa-associated glycoproteins including Fibrillin 1 (FBN1), Vitronectin (VTN) and Hemicentin 2 (HMCN2). A multi-marker panel composed of urinary PSA, VTN, HMCN2, CD97 achieved an AUC of 0.78 (p=2.69 × 10-9) for distinguishing AG-PCa from cancer-negative & Gleason 6. Analysis of differentially abundant glycopeptides in pre- and post-DRE samples showed that compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas immune cell-related proteins were enriched in post-DRE urine samples. CONCLUSIONS: Comparisons between post-DRE and pre-DRE urine specimens for glycoproteins have shown that pre-DRE samples hold promise for a non-invasive and simple early option for AG-PCa detection in patients. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant prostate cancer. Source of Funding: NCI/EDRN IAA No. ACN 17005-001-0000011 (Gregory Chesnut) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Indu Kohaar More articles by this author Yuefan Wang More articles by this author Tung-Shing Mamie Lih More articles by this author Naseruddin Höti More articles by this author Lori Sokoll More articles by this author Gregory Chesnut More articles by this author Gyorgy Petrovics More articles by this author Hui Zhang More articles by this author Expand All Advertisement PDF downloadLoading ...

レジオネラ肺炎を契機に発症したAcute–on–chronic liver failureの救命例(A case of acute–on–chronic liver failure caused by Legionella pneumonia)

レジオネラ肺炎は，多臓器不全を合併し致死的な経過をたどることがある。今回，ACLFに伴う肝性脳症を合併するも，人工肝補助療法を導入し，救命し得た症例を経験したので報告する。症例は50歳の男性で，高度意識障害と多臓器不全のため近隣病院から転院搬送された。搬入時より意識レベルはJCS III–300であり，血液検査でアンモニアが高値であった。肝性脳症と診断し，直ちにon–line HDFによる人工肝補助療法を開始した。第2病日に尿中レジオネラ抗原が陽性となったことから，レジオネラ肺炎と診断し，それに伴って多臓器不全を発症した状態であると判断した。抗生剤については，メロペネム，レボフロキサシン，アジスロマイシンを投与した。凝固障害に対しては，適宜輸血を実施した。合計3回のon–line HDFとCHDFを交互に実施し，緩徐に意識レベルの改善が得られ，第5病日には意識清明となった。第8病日にICUを退出し，第20病日に転院した。ACLFは，最近定義された新しい疾患概念であり，代償性あるいは非代償性肝硬変に増悪因子が加わって，高度の肝機能異常を呈する病態である。治療については症候に対する対症療法が中心であり，本症例では人工肝補助療法を導入したことで覚醒が得られ，救命に寄与したと考えられた。 Legionella pneumonia may be complicated by multiple organ failure and may result in death. We herein report a case of hepatic encephalopathy associated with acute–on–chronic liver failure, which was successfully rescued by artificial liver support therapy. A 50–year–old man was transferred from a nearby hospital due to severe disturbance of consciousness and multiple organ failure. His level of consciousness was Japan coma scale III–300, and a blood test revealed a high level of ammonia. Hepatic encephalopathy was diagnosed as the cause of consciousness disturbance, and artificial liver support therapy with on–line hemodiafiltration was started immediately. On Day 2, Legionella pneumonia was diagnosed because urinary Legionella antigen was positive. For antibiotics, meropenem, levofloxacin, and azithromycin were administered. Blood transfusion was performed as needed for coagulopathy. The patient’s level of consciousness gradually improved, and he became lucid on Day 5. He was discharged from the intensive care unit on Day 8 and transferred to another hospital on Day 20. We believe that the rapid introduction of artificial liver support therapy enabled the patient to regain consciousness. レジオネラ肺炎は，多臓器不全を合併することで，致死的な経過をたどることがある。アルコール多飲歴が感染のリスクであるため，大酒家であればその発症に注意を払う必要がある。一方，大酒家は肝硬変に罹患していることが多く，acute–on–chronic liver failure（ACLF）を発症することで，慢性肝不全が急激に進行する可能性がある。今回，レジオネラ肺炎の感染を契機にACLFを発症し肝性脳症に陥るも，on–line hemodiafiltration（HDF）による人工肝補助療法を導入することで，覚醒が得られた症例を経験したので報告する。 本論文に倫理委員会の承諾は必要がない。また本論文は個人情報保護法に基づいて匿名化がなされ，患者またはその家族より論文の出版に関する同意を得ている。 患 者：50歳の男性 主 訴：なし（高度意識障害） 既往歴：急性腹膜炎で手術歴あり，C型肝炎ウイルス（hepatitis C virus: HCV）感染後 sustained virological response，アルコール依存症（精神科病院に入院歴あるも通院は自己中断） 内服歴：常用薬なし。健康食品，サプリメントや漢方薬の使用なし 家族歴：肝疾患の家族歴なし 生活歴：温泉や循環式風呂の入浴なし。加湿器の使用なし。飲酒はアルコール度数9%の缶チューハイ2,500mL/day。喫煙は20本/dayを30年間。アレルギー歴なし。生肉の摂取なし。職業は土木建築業。両肩から両前腕にかけて刺青あり 現病歴：搬送数日前から車上生活を送っていた。搬送当日，河川敷に本人の車両が放置されており，警察官が周囲を捜索したところ，車両から約400m離れた土手で倒れている本人を発見し救急要請された。全身に明らかな外傷は認めず，車内には飲酒後と思われる空き缶が散在していた。過量服薬や違法薬物の使用の痕跡はなかった。直近二次病院に搬送されたが，Japan Coma Scale（JCS）III–300の高度意識障害と黄疸があり，採血では肝機能障害，腎機能障害，凝固障害，電解質異常を認めた。体幹部の単純computed tomography（CT）では両側スリガラス陰影と脂肪肝を疑わせる肝臓の斑状低吸収域を認めたが，明らかな胸腹水は認めなかった。前医では対応困難であり，多臓器不全に対する集中治療目的に当院の救命救急センターに緊急転院搬送となった。 入院時現症：身長168cm，体重70.7kg，body mass index 25.0kg/m2，意識レベル Glasgow Coma Scale（GCS）E1V1M1，体温36.9度，血圧135/81mmHg，脈拍110/min・整，呼吸数30/min，SpO2 98%（酸素マスク5L/min）であった。瞳孔は左右同大5mmで対光反射は両側迅速，眼球結膜に黄染を認めた。胸部聴診では，心音は整で雑音はなく，両側胸部でcoarse cracklesを聴取した。腹部は膨満，軟で腹部正中に手術痕あり，右季肋部に肝臓を三横指触知し，波動は認めず，クモ状血管腫や女性化乳房も認めなかった。両側下腿に軽度の圧痕性浮腫を認めた。 入院時検査所見：当院で再検した血液検査（Table 1）では，貧血，凝固障害，肝機能障害，腎機能障害，電解質異常と多臓器不全を呈していた。新型コロナウイルス感染症の迅速抗原検査およびpolymerase chain reaction（PCR）検査は陰性であった。HCV ribonucleic acid（RNA）は陰性であった。また，尿中薬物検査キットもすべて陰性であった。頭部CTでは意識障害を来しうる脳出血や腫瘤性病変は認めなかった。体幹部単純CT（Fig. 1）では，両側上葉優位に浸潤影や網状影を認め，下葉に淡い濃度上昇を伴う陰影を認めたが，明らかな胸水貯留は指摘できなかった。肝形態は保たれており，肝臓周囲には腹水は認めず，胆嚢の浮腫性変化も認めなかった。入院時の血液検査結果では，FIB–4スコアは20.9点で，C型肝硬変の判別式は20点であった。 CT scans of the patient. A: Day 1, B: Day 7, C: Day 15 The abnormal chest opacity gradually improved. B showed ascites accumulation (white arrow), but C showed improvement. 入院後経過（Fig. 2）：病歴や所見からは元々アルコール性慢性肝硬変が背景にあり，何らかの要因で急性増悪し，ACLFおよび肝性脳症を来したものと考えた。肝性脳症については，犬山分類 grade Vであり，右内頸静脈からバスキュラーアクセスを確保し，直ちにon–line HDF（透析膜：FIX250E；ニプロ，血流量200mL/min，透析液流量500mL/min，補充液流量5,000mL/hour）を開始した。On–line HDFに伴い，血清カリウムとリンの低下が懸念され，適宜補正を行った。貧血と凝固障害に対しては，輸血を行い，ビタミンK製剤の投与を行った。消化管出血の懸念があったため，経鼻胃管は挿入せずに，経肛門的にラクツロースの注腸を開始した。分岐鎖アミノ酸製剤の投与については，窒素負荷につながり，肝性脳症を助長する可能性があると判断したため実施しなかった。On–line HDF終了後は，continuous hemodiafiltration（透析膜：セプザイリス；バクスター，血流量100mL/min，補充液流量400mL/min，排液量800mL/min，透析液流量400mL/min，以下CHDF）での血液浄化を開始した。敗血症の可能性は否定できず，各種培養を採取した後に，メロペネム（meropenem: MEPM）の投与を開始した。呼吸不全については，マスクでの酸素投与のみで酸素化が維持可能であり，努力呼吸も認めなかったことから，気管挿管や人工呼吸器管理は見送った。肺炎像の鑑別目的に，第2病日に実施した尿中レジオネラ抗原（リボテスト；旭化成ファーマ）が陽性となったため，レジオネラ肺炎と確定診断し，病態としてレジオネラ肺炎が契機となりACLFを発症したものと考えた。また，レボフロキサシン（levofloxacin: LVFX）の静注を開始した。培養検査については，当院ではbuffered charcoal yeast extract（BCYE）培地を常備しておらず，ヒメネス染色も外部発注の検査となること，尿中抗原陽性であれば，感染症法の四類感染症の定義を満たすことから実施しなかった。喀痰loop–mediated isothermal amplification（LAMP）法については外注であったが提出し，結果，良好な喀痰が得られなかったことと，LVFXを投与後に検体を採取した影響のためか陰性であった。一方で，第2病日のアンモニアが280μg/dLと増悪していたため，分岐鎖アミノ酸製剤は引き続き投与せず，2回目のon–line HDFを導入した。On–line HDF後の採血では，アンモニアが130μg/dLと改善しており，意識レベルも改善を認めた。第3病日に，重症のレジオネラ肺炎と判断し，LVFXに加えて，アジスロマイシン（azithromycin: AZM）の静注を開始し，AZMについては合計5日間投与した。同日の採血では，アンモニアは改善傾向であったが，依然として意識障害が残存していたため，3回目のon–line HDFを実施した。その後は乏尿が続いていたため，腎代替療法としてCHDFによる除水を継続した。3回目のon–line HDF施行後より，徐々に意識レベルは改善し，第4病日には軽度の見当識障害を認めるのみとなった。黄疸については，皮膚掻痒感の訴えに対し軟膏塗布での対症療法，経過観察とした。第6病日より食事（蛋白20g制限食）とリファキシミンの内服を開始した。第7病日に体幹部CTを再検査したところ，肺炎像については改善傾向を認め，新たに腹水が貯留していた。同日，自尿が増加傾向であったため，CHDFから離脱した。全身状態として経過が順調であったことから，第8病日にICUを退室した。また，入院時に採取した培養検査がすべて陰性であったことを確認し，MEPMの投与は終了した。第12病日にLVFXは内服へ移行し，静注と内服で合計21日間の抗生剤治療を予定した。一般床に転棟後は，羽ばたき振戦や異常行動を認めることなく経過した。第15病日に体幹部CTを再検し，肺炎像と腹水が消退傾向であることを確認した。第20病日に肝不全や黄疸に対する治療継続目的，およびリハビリテーション継続目的に，独歩で近隣病院に転院した。 Clinical course of the patient. i.v: intravenous drip, p.o: per os 今回，ACLFを合併し，肝性脳症により昏睡状態に陥るも，on–line HDFを用いた人工肝補助療法を導入することで，覚醒が得られたレジオネラ肺炎の1例を経験した。我々が渉猟し得た限りでは，本邦で類似症例の報告はなく，本症例はレジオネラ肺炎が契機となってACLFを合併し，on–line HDFを用いることで救命し得た初の報告である。 レジオネラ菌（Legionella pneumophilla）は，1976年の米国在郷軍人会で発生した重症肺炎の原因菌として，1977年に初めて同定された好気性ブドウ糖非発酵グラム陰性桿菌である1。世界中の土壌中や環境水中に存在し，埃やエアロゾルとして吸入することで感染が成立する。市中肺炎のみならず，院内肺炎の起因菌としても重要である。細胞内寄生菌のため，細胞内へ移行し効果を発揮するβ–ラクタム系の抗菌薬は無効であり，早期の治療介入のためには鑑別すべき疾患として挙げることが必要である。ところが，確定診断のためにはヒメネス染色やBCYE培地での細菌培養，喀痰LAMP法といった，施設によっては外部発注での検査が必要となることが課題であった。近年ではその報告件数は増加傾向となっており2，要因として，1999年に感染症法の四類感染症に指定されたことや，2003年に尿中抗原検査が保険適応となったことが挙げられる。 重症度という点に着目すると，レジオネラ肺炎はしばしば多臓器不全を合併し，致死的な経過をたどることがある2。高柳らの報告によれば，死亡は65例中6例で，死因として敗血症性ショックや腎不全，播種性血管内凝固，多臓器不全の併発によるものであった2。とくに，多臓器不全を合併した3例中2例が死亡しており，レジオネラ肺炎に多臓器不全を合併した場合の致死率は極めて高いことが推察される。また，レジオネラ肺炎の発症リスクとして，高齢，男性，免疫抑制状態，慢性肺疾患，アルコール多飲歴，悪性腫瘍，鉄過剰症，tumor necrosis factor–α（TNF–α）治療歴，および喫煙が挙げられている3。本症例では，アルコール多飲歴やアルコール依存症の既往歴を認めていたことから，確定診断はされていないものの，基礎疾患としてアルコール性慢性肝硬変の存在が示唆され，発症リスクが高かったと推測された。また，肝硬変による免疫不全状態と考えれば，重症化しやすい素因も併せ持っていたと推測された。すなわち，アルコール多飲歴，肝硬変，レジオネラ肺炎の三者が，相互に悪影響を及ぼしたため，重症化に至ったと考えられた。 そのような背景のなかで，本症例ではレジオネラ肺炎が契機となってACLFを発症したと考えた。そもそも肝不全とは，肝細胞の減少ないし機能低下によって生体の恒常性が維持できなくなることであり，発症から肝不全に至るまでの期間で，急性，遅発性，慢性に分類されている4。急性肝不全とは「肝炎の発症から8週間以内に，高度の肝機能障害に基づいて昏睡II度以上の昏睡を来し，プロトロンビン時間が40%以下を示すもの」と定義される4。一方で，ACLFとは，「Child–Pughスコアが5～9点の代償性ないし非代償性肝硬変に，アルコール多飲，感染症，消化管出血，原疾患増悪などの増悪因子が加わって，28日以内に高度の肝機能異常に基づいて，プロトロンビン時間INRが1.5以上ないし同活性が40%以下で，血清総ビリルビン値が5.0mg/dL以上を示す症例」と厚生労働省の研究班により2018年に定義された5。急性肝不全とACLFは，正常肝あるいは肝予備能が正常の慢性肝疾患が背景にあるかどうか，という点で差別化された。診断に至るまでの因果関係として，急性肝不全が先行し，全身状態が悪化した後にレジオネラ肺炎を二次的に合併した，という可能性についても考慮されたが，レジオネラ肺炎が多臓器不全を発症しうる2という点を根拠に，本症例では，元々アルコール多飲に伴った肝硬変が存在し，レジオネラ肺炎を契機にACLFを発症したものと考えた。 ACLFの治療については，肝移植を除けば特異的かつ決定的なものはない6。原因に対する治療や，症候に対する対症療法が基本となる7。アルコール性慢性肝炎に準じたステロイドの投与については考慮したが，本症例では実施しなかった。肺野の異常陰影が，間質性肺炎の急性増悪であった場合，なおのことステロイドの投与が考慮されたが，レジオネラ肺炎の診断に至ったためにその必要性が低下し，人工肝補助療法での治療が奏功しない場合に，その実施を検討する方針としていたためである。血漿交換（plasma exchange: PE）についても，まずはon–line HDFで肝性脳症治療を進め，覚醒が得られない場合に実施を検討する方針としていた。幸い，on–line HDFとCHDFによる治療が奏功したため，血漿交換の導入は不要であった。肝移植については，現実的な問題として多臓器不全を呈しており，全身麻酔に耐えうるかが不明であったこと，背景にアルコール依存症があり，断酒もできていないことから，適応はないと判断した。 急性肝不全の内科的治療における両輪は，蛋白合成能（とくに血液凝固因子）の補助と解毒能の代替である8。前者については，新鮮凍結血漿（fresh frozen plasma: FFP）の輸血やアルブミン投与，ビタミンK製剤の補充を行うことが基本となる。本症例では，プロトロンビン時間40%を目標に適宜FFPを投与した。後者については，解毒すべき物質，すなわち肝性脳症の原因物質の排除が必要となる。本邦では，欧米と比較して肝移植のドナーが見つかりにくいという背景から人工肝補助療法が発展してきた9。肝性脳症の原因物質の代表の一つにアンモニアがあり10，アンモニアは肝性脳症患者の主たる死亡原因である脳浮腫および脳ヘルニアを惹起する可能性が示唆されている11。すなわち，人工肝補助療法の最大の目的は，肝性脳症から覚醒させ，意識障害を改善させることにある。アンモニアは分子量17g/moLと低分子であるため，小分子除去に効率の良い血液透析（hemodialysis: HD）が有効と考えられるが，実際にはHDでの肝性脳症の覚醒率は40%程度である12。これは，アンモニア以外に中分子の肝性脳症物質が関与しているためと考えられている（中分子仮説）が，具体的な物質の同定までは至っていない13。ほか，PE，血液濾過（hemofiltration: HF）での覚醒率は37.5%，78%程度である12。単独での実施は効果に乏しく，両者の利点を併せ持ったHDFが有効と考えられる。とくに，中央配管から供給される純水を透析液と置換液として使用し，前希釈法によるon–line HDFが効率的かつ経済的であるという報告が挙がっている14。本邦では，PEとHDFによるコンビネーション法が主流とされる15が，本症例では，まずon–line HDFを実施し，効果が得られない場合にPEを併用する方針としていた。結果，PEは回避することができ，on–line HDF単独でも良好な覚醒が得られ，脳ヘルニアに至ることなく経過した。覚醒率が高いということは，ICU入室期間の短縮にもつながる。合併症や続発症の低減などによる要素が，救命に寄与したと考えられた。本症例を通して，急性肝不全による肝性脳症のみならず，ACLFによる肝性脳症に対しても，on–line HDFによる人工肝補助療法が効果的であることが示唆された。 人工肝補助療法におけるon–line HDFの注意すべき点の一つとして，透析液が腎不全用であることが挙げられる16。すなわち，カリウム，リンが透析液中に不足しており，重炭酸が過剰に含まれている。アンモニアと同様に，カリウムとリンも小分子であるため，on–line HDFの開始に伴い急激に低下する可能性があり，注意が必要である。本症例では，HDF開始前と開始後約2時間が経過した時点，終了後の3ポイントで血液検査を実施し，カリウムとリンの値を逐一確認し，適宜補正を行った。また，薬剤や栄養についても影響を受けるため注意が必要と考えられる。本症例では，とくに抗生剤治療において，濃度依存性のLVFXと腎機能に応じて調整不要のAZMが治療の主軸であったため，on–line HDFの影響を考慮することなく治療を進めることが可能であった。 レジオネラ肺炎を契機としてアルコール性慢性肝硬変を背景にACLFを合併し，肝性脳症に陥った症例を経験した。肝性脳症に対して，on–line HDFによる人工肝補助療法を導入したことで覚醒が得られ，救命し得たと考えられた。 本論文における利益相反はない。

Disseminated Blastomycosis in a Previously Stable Crohn's Disease Patient on Infliximab Therapy

Abstract Reactivation of granulomatous diseases is a well-documented risk of biologic therapy. This case highlights a patient well controlled on chronic infliximab therapy, developing symptoms consistent with disease progression. The patient underwent a surgical laparoscopy given concern of small bowel obstruction in which diffuse, peritoneal nodularity was seen. Further staining revealed broad-budding yeast and blastomyces urinary antigen resulted as positive. The patient was treated for disseminated blastomycosis, and his symptoms completely resolved.

UTILITY OF URINE ANTIGEN TESTING FOR DIAGNOSIS OF BLASTOMYCOSIS IN NONDOMESTIC FELIDS.

Blastomycosis caused by the fungus Blastomyces dermatitidis has been reported to cause disease in numerous species of nondomestic felids. Diagnosis of blastomycosis in domestic species often relies on the combination of clinical signs, radiographic findings, and commercial urinary antigen testing. In this report, the sensitivity, specificity, and positive and negative predictive values for urine blastomyces antigen testing for use in nondomestic felids were examined and compared with findings on postmortem examination. The study showed a sensitivity of 100%, specificity of 91.86%, positive predictive value of 50%, and negative predictive value of 100% for urine antigen testing. Furthermore, radiographic and hematologic findings were compared with those of animals diagnosed with blastomycosis. Radiographic evidence consistent with blastomycosis was found in those animals diagnosed via urine antigen testing, but no significant differences in plasma biochemistry parameters between diseased and nondiseased animals were found. This study provides evidence that a positive blastomycosis antigenuria test result should be combined with other diagnostic methods to confirm the presence of infection with B. dermatitidis, whereas a negative antigenuria test result is 100% effective in predicting the absence of disease.