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1.
Arq. ciências saúde UNIPAR ; 26(3): 1360-1375, set-dez. 2022.
Article in Portuguese | LILACS | ID: biblio-1402290

ABSTRACT

A ocorrência das infecções do trato urinário (ITU) causadas por leveduras do gênero Candida estão aumentando consideravelmente nas últimas décadas, sendo a Candida albicans a mais comumente diagnosticada como causadora deste tipo de infecções. Contudo, outras espécies, como exemplo da Candida tropicalis, estão emergindo como preocupantes causadores da doença. Neste sentido, o objetivo do presente trabalho é revisar os aspectos relacionados com as ITU causadas por leveduras do gênero Candida. Foi realizada uma pesquisa na base de dados PubMed, buscando artigos sobre a epidemiologia, patogenia e tratamento das ITU causadas por leveduras do gênero Candida. As espécies de Candida são os fungos patogênicos oportunistas mais relevantes causadores de infecções nosocomiais e podem causar infecção no trato urinário, tanto inferior (ureteres, bexiga e uretra) quanto superior (rins), principalmente em pacientes imunocomprometidos. Existem alguns fatores predisponentes, como gênero feminino, idade avançada, diabetes mellitus, hospitalização prolongada, imunossupressão, gravidez, hipertensão, neutropenia, cálculos renais, infecções nosocomiais, terapia antibiótica e procedimentos, como a cateterização, que atuam como facilitadores das ITU por Candida spp. A doença pode ocorrer de forma assintomática, porém, pode evoluir para casos mais graves com comprometimento sistêmico em situações de candidemia que pode causar a morte do paciente, principalmente se tratando de indivíduos imunocomprometidos. Sendo assim, devido ao risco existente, a doença não pode ser negligenciada e um diagnóstico preciso e um tratamento adequado devem ser estabelecidos.


The occurrence of urinary tract infections (UTI) caused by yeasts of the genus Candida has increased considerably in recent decades, with Candida albicans being the most commonly diagnosed as causing this type of infections. However, other species, such as Candida tropicalis, are emerging as worrisome causes of the disease. In this sense, the objective of the present paper is to review the aspects related to the UTI caused by yeasts of the genus Candida. A search was carried out in the PubMed database, searching for articles on the epidemiology, pathogenesis and treatment of UTI caused by yeasts of the genus Candida. Candida species are the most relevant opportunistic pathogenic fungi that cause nosocomial infections and can cause both lower (ureters, bladder and urethra) and upper (kidneys) urinary tract infections, especially in immunocompromised patients. There are some predisposing factors, such as female gender, advanced age, diabetes mellitus, prolonged hospitalization, immunosuppression, pregnancy, hypertension, neutropenia, kidney stones, nosocomial infections, antibiotic therapy and procedures, such as catheterization, that act as facilitators of UTI by Candida spp. The disease can occur asymptomatically, however, it can progress to more severe cases with systemic involvement in situations of candidemia that can cause the death of the patient, especially in immunocompromised individuals. Therefore, due to the existing risk, the disease cannot be neglected and an accurate diagnosis and adequate treatment must be established.


La aparición de infecciones del tracto urinario (ITU) causadas por levaduras del género Candida ha aumentado considerablemente en las últimas décadas. Candida albicans es la infección por levaduras más comúnmente diagnosticada. Sin embargo, otras especies, como la Candida tropicalis, están surgiendo como causa preocupante de la enfermedad. En este sentido, el objetivo del presente trabajo es revisar los aspectos relacionados con la ITU causada por levaduras del género Candida. Se realizó una búsqueda en la base de datos PubMed, buscando artículos sobre la epidemiología, la patogénesis y el tratamiento de la ITU causada por levaduras del género Candida. Las especies de Candida son los hongos patógenos oportunistas más relevantes que causan infecciones nosocomiales y pueden provocar infecciones del tracto urinario inferior (uréteres, vejiga y uretra) y superior (riñones), especialmente en pacientes inmunodeprimidos. Existen algunos factores predisponentes, como el sexo femenino, la edad avanzada, la diabetes mellitus, la hospitalización prolongada, la inmunosupresión, el embarazo, la hipertensión, la neutropenia, los cálculos renales, las infecciones nosocomiales, la terapia con antibióticos y los procedimientos como el cateterismo, que actúan como facilitadores de la ITU por Candida spp. La enfermedad puede presentarse de forma asintomática, pero puede evolucionar a casos más graves con afectación sistémica en situaciones de candidemia que pueden causar la muerte del paciente, especialmente en individuos inmunodeprimidos. Por lo tanto, debido al riesgo existente, no se puede descuidar la enfermedad y se debe establecer un diagnóstico preciso y un tratamiento adecuado.


Subject(s)
Urinary Tract Infections/complications , Candida albicans/pathogenicity , Candida tropicalis/pathogenicity , Pyelonephritis/complications , Urinary Tract/injuries , Cross Infection/complications , Epidemiology/statistics & numerical data , Immunocompromised Host/physiology , Biofilms , Cystitis/complications , Candidemia/complications , Hospitalization
2.
Eur J Pharmacol ; 925: 174999, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35525311

ABSTRACT

Vitexin-2-O-rhamnoside (VR) is an important active substance in hawthorn, which is widely used as a food or functional food raw material; however, its immunomodulatory activities have not been extensively studied. In this study, BALB/c mice immunocompromised by cyclophosphamide (CY) were used as models to explore the effects of VR on the immunity and antioxidant capacity of mice. The results revealed that VR can restore weight to the immunosuppressed mice to varying degrees, improve spleen and thymus injury, and restore peripheral blood levels. Furthermore, it can effectively promote the proliferation of T and B lymphocytes, natural killer (NK) and cytotoxic T lymphocyte (CTL) cell activities, and the secretion and mRNA expression of cytokines IFN-γ, IL-2, IL-6, and IL-12 to 0.36, 0.34, 50.25%, 45.74%, 28.36 pg/mL or 0.68, 31.81 pg/mL or 0.74, 20.40 pg/mL or 0.75, and 19.81 pg/mL or 0.55, respectively. Moreover, it can upregulate the phosphorylation level of PI3K/Akt signaling pathway in mice immunosuppressed by CY, increase the activities of glutathione peroxidase (GSH-Px), chloramphenicol acetyltransferase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and decrease the level of malondialdehyde (MDA). This study provides a theoretical and experimental basis for the research and development of health products with targeted efficacy, and the development of diversified products in the hawthorn deep-processing industry.


Subject(s)
Antioxidants , Immunocompromised Host , Immunosuppression Therapy , Signal Transduction , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Catalase/metabolism , Cyclophosphamide/adverse effects , Cyclophosphamide/pharmacology , Flavonoids/pharmacology , Glycosides/pharmacology , Immunocompromised Host/drug effects , Immunocompromised Host/physiology , Immunosuppression Therapy/adverse effects , Mice , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology
3.
J Med Virol ; 94(1): 99-109, 2022 01.
Article in English | MEDLINE | ID: mdl-34570905

ABSTRACT

A severe pandemic of Coronavirus Disease (COVID-19) has been sweeping the globe since 2019, and this time, it did not stop, with frequent mutations transforming into virulent strains, for instance, B.1.1.7, B.1.351, and B.1.427. In recent months, a fungal infection, mucormycosis has emerged with more fatal responses and significantly increased mortality rate. To measure the severity and potential alternative approaches against black fungus coinfection in COVID-19 patients, PubMed, Google Scholar, World Health Organization (WHO) newsletters, and other online resources, based on the cases reported and retrospective observational analysis were searched from the years 2015-2021. The studies reporting mucormycosis with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) coinfection and/or demonstrating potential risk factors, such as a history of diabetes mellitus or suppressed immune system were included, and reports published in non-English language were excluded. More than 20 case reports and observational studies on black fungus coinfection in COVID-19 patients were eligible for inclusion. The results indicated that diabetes mellitus, hyperglycemic, and immunocompromised COVID-19 patients with mucormycosis were at a higher risk. We found that it was prudent to assess the potential risk factors and severity of invasive mycosis via standardized diagnostic and clinical settings. Large-scale studies need to be conducted to identify early biomarkers and optimization of diagnostic methods has to be established per population and geographical variation. This will not only help clinicians around the world to detect the coinfection in time but also will prepare them for future outbreaks of other potential pandemics.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Mucormycosis/epidemiology , Mucormycosis/mortality , SARS-CoV-2/isolation & purification , Diabetes Mellitus/pathology , Humans , Hyperglycemia/pathology , Immunocompromised Host/physiology , Mucorales/growth & development , Mucorales/isolation & purification , Mucormycosis/pathology , Retrospective Studies , Risk Factors
5.
Medicine (Baltimore) ; 100(28): e26656, 2021 Jul 16.
Article in English | MEDLINE | ID: mdl-34260570

ABSTRACT

RATIONALE: Cryptococcal infection has been documented in immunocompromised patients. AIDS and renal transplant recipients account for majority of the cases. Most cases present with central nervous system or disseminated disease, with only few presenting soft tissue, bone, and joint manifestations. PATIENT CONCERNS: We present a case of soft tissue mass in a 66-year-old female renal transplant recipient and that of arthritis in a 64-year-old immunocompetent man who presented pseudogout arthropathy. Chest radiographies of both cases were negative. Biopsy revealed cryptococcal organisms. Blood culture or cerebrospinal fluid sampling indicated positive results for cryptococcal antigen. DIAGNOSIS: Cryptococcus neoformans was recovered in the wound culture. INTERVENTIONS: The patients received intravenous fluconazole and flucytosine, followed by oral fluconazole administration. OUTCOMES: Symptomatic improvements were achieved and no subsequent relapses were observed. LESSONS: The authors experienced 2 cases of cryptococcosis with very unusual clinical presentation. Early clinical suspicion and serum cryptococcal antigen testing can help in rapid appropriate diagnosis in immunocompetent as well as immunocompromised patients even in the absence of pulmonary involvement.


Subject(s)
Abscess/microbiology , Cryptococcosis/diagnosis , Abscess/diagnosis , Abscess/drug therapy , Aged , Antifungal Agents/therapeutic use , Arthritis/diagnosis , Arthritis/physiopathology , Cryptococcosis/drug therapy , Cryptococcosis/physiopathology , Cryptococcus neoformans , Diagnosis, Differential , Female , Fluconazole/therapeutic use , Flucytosine/therapeutic use , Humans , Immunocompromised Host/physiology , Kidney Transplantation , Male , Middle Aged
6.
Expert Rev Vaccines ; 20(8): 1013-1025, 2021 08.
Article in English | MEDLINE | ID: mdl-34180347

ABSTRACT

INTRODUCTION: Several vaccine candidates have been developed using different platforms, including nucleic acids (DNA and RNA), viral vectors (replicating and non-replicating), virus-like particles, peptide-based, recombinant proteins, live attenuated, and inactivated virus modalities. Although many of these vaccines are undergoing pre-clinical trials, several large clinical trials investigating the clinical efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines have produced promising findings. AREAS COVERED: In this review, we provide a status update on COVID-19 vaccines currently undergoing clinical trials and discuss issues of concern beyond vaccine efficacy and safety, including dosing regimens, the mixed vaccine strategy, prior severe acute respiratory syndrome coronavirus-2 infection, antibody levels, cellular immunity and protection, variants of concern, COVID-19 vaccine distribution, vaccination willingness, herd immunity, immunity passports, and vaccine indications. EXPERT OPINION: Four vaccines have obtained emergency use authorization, 87 are at the clinical development stage, and 186 are in pre-clinical development. While the knowledge and development of COVID-19 vaccines is rapidly expanding, the benefits of COVID-19 vaccines must outweigh the potential risks of adverse events. To combat the COVID-19 pandemic, clinicians should consistently update COVID-19-associated information, and healthcare authorities and manufacturers should work together to provide adequate and appropriate vaccinations for the prevention of COVID-19. PLAIN LANGUAGE SUMMARY: What is the context?Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic: the coronavirus disease 2019 (COVID-19) outbreak. The development and implementation of the COVID-19 vaccine could be an important measure to control the COVID-19 pandemic.What is new?Several phase 3 clinical trials have demonstrated the effectiveness and safety of COVID-19 vaccines for the prevention of SARS-CoV-2 infections. Several COVID-19 vaccines have obtained emergency use authorization and been implemented in many countries. Although concerns regarding unusual blood clots and low platelet counts have been raised, the benefits of COVID-19 vaccines outweigh the potential risks of adverse events.What is the impact?Except for children, the COVID-19 vaccine is recommended for all people, including those pregnant or immunocompromised. Healthcare authorities should advise people receiving the vaccine that they must seek medical attention if they have associated thromboembolism and thrombocytopenia symptoms. More studies are necessary to determine the appropriate vaccine dose and regimen strategy, as well as the effectiveness of COVID-19 vaccines against variants of concerns. A global effort must be made to achieve widespread vaccination and herd immunity.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Patient Safety , Animals , COVID-19/epidemiology , Clinical Trials, Phase III as Topic/methods , Fatigue/chemically induced , Female , Fever/chemically induced , Headache/chemically induced , Humans , Immunocompromised Host/drug effects , Immunocompromised Host/physiology , Male , Pregnancy , Randomized Controlled Trials as Topic/methods , Treatment Outcome
7.
J Hepatol ; 75(5): 1128-1141, 2021 11.
Article in English | MEDLINE | ID: mdl-34171432

ABSTRACT

BACKGROUND & AIMS: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression. METHODS: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations. RESULTS: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC. CONCLUSIONS: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy. LAY SUMMARY: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations.


Subject(s)
ErbB Receptors/immunology , Gallbladder Neoplasms/immunology , Immunocompromised Host/physiology , Midkine/adverse effects , Cell Proliferation/genetics , China/epidemiology , ErbB Receptors/antagonists & inhibitors , Gallbladder Neoplasms/epidemiology , Gallbladder Neoplasms/physiopathology , Humans , Midkine/genetics , Sequence Analysis, RNA/methods , Sequence Analysis, RNA/statistics & numerical data , Signal Transduction/genetics , Single-Cell Analysis/methods , Single-Cell Analysis/statistics & numerical data , Exome Sequencing/methods , Exome Sequencing/statistics & numerical data
8.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: mdl-34117116

ABSTRACT

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Subject(s)
COVID-19 , Drug Repositioning , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Immunotherapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Comorbidity , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/immunology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompromised Host/physiology , Immunotherapy/adverse effects , Immunotherapy/methods , Immunotherapy/statistics & numerical data , Mortality , Pandemics , Prognosis , Rheumatic Diseases/epidemiology , SARS-CoV-2/physiology , Transplant Recipients/statistics & numerical data
9.
AIDS Res Ther ; 18(1): 28, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33952300

ABSTRACT

Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.


Subject(s)
Anti-Retroviral Agents/therapeutic use , COVID-19/pathology , Coinfection/pathology , HIV Infections/pathology , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Adult , COVID-19/complications , COVID-19/immunology , Coinfection/immunology , Cytokines/blood , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/immunology , Humans , Immunocompromised Host/immunology , Immunocompromised Host/physiology , Lymphopenia/pathology , Middle Aged , Treatment Outcome , COVID-19 Drug Treatment
10.
Int J Mol Sci ; 22(7)2021 Mar 31.
Article in English | MEDLINE | ID: mdl-33807229

ABSTRACT

Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor-ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor-ligand interactions.


Subject(s)
Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Uveitis, Anterior/metabolism , Adult , Aged , Aged, 80 and over , CD57 Antigens/genetics , CD57 Antigens/immunology , Cohort Studies , Cytomegalovirus/immunology , Cytomegalovirus/pathogenicity , Cytomegalovirus Infections/immunology , Female , Genes, MHC Class I/genetics , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunocompromised Host/immunology , Immunocompromised Host/physiology , Killer Cells, Natural/physiology , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily C/genetics , NK Cell Lectin-Like Receptor Subfamily C/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Receptors, KIR/genetics , Transplantation, Homologous/adverse effects , Uveitis, Anterior/genetics , Uveitis, Anterior/virology
11.
PLoS One ; 16(2): e0246296, 2021.
Article in English | MEDLINE | ID: mdl-33539407

ABSTRACT

OBJECTIVE: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. METHODS: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). RESULTS: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016). CONCLUSIONS: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.


Subject(s)
Pneumonia, Pneumocystis/mortality , Pneumonia, Pneumocystis/physiopathology , Aged , Female , Hospital Mortality , Humans , Immunocompromised Host/physiology , Male , Middle Aged , Pneumocystis carinii/pathogenicity , Pneumonia, Pneumocystis/epidemiology , Prognosis , Proportional Hazards Models , Republic of Korea/epidemiology , Retrospective Studies
13.
Ann Hematol ; 100(1): 1-10, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33009935

ABSTRACT

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection with high mortality rate usually seen in the context of immunosuppression. Although cases have been reported largely in patients with HIV/AIDS, following the use of monoclonal antibodies and occasionally in haematological malignancies, there is no review to date of patients with smouldering or treated myeloma who developed PML. Here, we conducted a literature search of PML cases in patients with multiple myeloma (MM), analyse patient and disease characteristics and describe the possible mechanisms that could lead to the development of PML. The lack of data and case reports until 2010 may indicate that PML in MM is underdiagnosed. Simultaneously, with an expanding field of new therapeutic options, patients with MM live longer, albeit continually immunosuppressed, and at risk of opportunistic infections. Emerging new treatments for PML in the horizon render the need to look out for this complication mandatory, and more case reports are needed to enrich our knowledge in this field.


Subject(s)
Immunocompromised Host/drug effects , Leukoencephalopathy, Progressive Multifocal/drug therapy , Leukoencephalopathy, Progressive Multifocal/immunology , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Humans , Immunocompromised Host/physiology , Immunologic Factors/metabolism , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Leukoencephalopathy, Progressive Multifocal/metabolism , Multiple Myeloma/metabolism
14.
Crit Care Med ; 48(10): e916-e926, 2020 10.
Article in English | MEDLINE | ID: mdl-32931197

ABSTRACT

OBJECTIVES: To describe the Children's Hospital Association's Improving Pediatric Sepsis Outcomes sepsis definitions and the identified patients; evaluate the definition using a published framework for evaluating sepsis definitions. DESIGN: Observational cohort. SETTING: Multicenter quality improvement collaborative of 46 hospitals from January 2017 to December 2018, excluding neonatal ICUs. PATIENTS: Improving Pediatric Sepsis Outcomes Sepsis was defined by electronic health record evidence of suspected infection and sepsis treatment or organ dysfunction. A more severely ill subgroup, Improving Pediatric Sepsis Outcomes Critical Sepsis, was defined, approximating septic shock. INTERVENTIONS: Participating hospitals identified patients, extracted data, and transferred de-identified data to a central data warehouse. The definitions were evaluated across domains of reliability, content validity, construct validity, criterion validity, measurement burden, and timeliness. MEASUREMENTS AND MAIN RESULTS: Forty hospitals met data quality criteria across four electronic health record platforms. There were 23,976 cases of Improving Pediatric Sepsis Outcomes Sepsis, including 8,565 with Improving Pediatric Sepsis Outcomes Critical Sepsis. The median age was 5.9 years. There were 10,316 (43.0%) immunosuppressed or immunocompromised patients, 4,135 (20.3%) with central lines, and 2,352 (11.6%) chronically ventilated. Among Improving Pediatric Sepsis Outcomes Sepsis patients, 60.8% were admitted to intensive care, 26.4% had new positive-pressure ventilation, and 19.7% received vasopressors. Median hospital length of stay was 6.0 days (3.0-13.0 d). All-cause 30-day in-hospital mortality was 958 (4.0%) in Improving Pediatric Sepsis Outcomes Sepsis; 541 (6.3%) in Improving Pediatric Sepsis Outcomes Critical Sepsis. The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated strengths in content validity, convergent construct validity, and criterion validity; weakness in reliability. Improving Pediatric Sepsis Outcomes Sepsis definitions had significant initial measurement burden (median time from case completion to submission: 15 mo [interquartile range, 13-18 mo]); timeliness improved once data capture was established (median, 26 d; interquartile range, 23-56 d). CONCLUSIONS: The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated feasibility for large-scale data abstraction. The patients identified provide important information about children treated for sepsis. When operationalized, these definitions enabled multicenter identification and data aggregation, indicating practical utility for quality improvement.


Subject(s)
Electronic Health Records/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Intensive Care Units, Pediatric/statistics & numerical data , Quality Improvement/organization & administration , Sepsis/therapy , Adolescent , Child , Child, Preschool , Female , Hospital Mortality/trends , Humans , Immunocompromised Host/physiology , Infant , Length of Stay/statistics & numerical data , Male , Organ Dysfunction Scores , Positive-Pressure Respiration , Reproducibility of Results , Sepsis/mortality , Severity of Illness Index , Shock, Septic/mortality , Shock, Septic/therapy
15.
Crit Care Med ; 48(9): e768-e775, 2020 09.
Article in English | MEDLINE | ID: mdl-32706556

ABSTRACT

OBJECTIVES: To assess the response to initial oxygenation strategy according to clinical variables available at admission. DESIGN: Multicenter cohort study. SETTING: Thirty French and Belgium medical ICU. SUBJECTS: Immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03-2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07-3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23-10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73-4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27-3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10-4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11-11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35-4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26-3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates. CONCLUSIONS: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.


Subject(s)
Critical Illness/therapy , Immunocompromised Host/physiology , Intubation, Intratracheal/statistics & numerical data , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Cross Infection/epidemiology , Humans , Intensive Care Units/statistics & numerical data , Length of Stay , Lung/pathology , Organ Dysfunction Scores , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/mortality , Severity of Illness Index
16.
Diagn Cytopathol ; 48(12): E10-E13, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32592614

ABSTRACT

Ascites due to Mycobacterium avium intracellulare (MAI) infection is extremely rare and associated with a poor outcome. The cytomorphology of this condition has not been previously reported. We present a unique case of a 45-year-old woman with iatrogenic immunodeficiency who developed MAI-associated chylous ascites. The ascitic fluid cytology showed numerous lymphocytes and foamy histiocytes with abundant intracytoplasmic MAI organisms. The diagnosis was confirmed by tissue biopsy showing MAI mesenteritis. It is important to consider MAI-associated ascites in the differential diagnosis whenever ascitic fluid shows a predominant population of lymphocytes and macrophages, especially in immunocompromised patients.


Subject(s)
Chylous Ascites/diagnosis , Chylous Ascites/etiology , Mycobacterium avium Complex/pathogenicity , Mycobacterium avium-intracellulare Infection/complications , Mycobacterium avium-intracellulare Infection/diagnosis , Chylous Ascites/microbiology , Chylous Ascites/pathology , Diagnosis, Differential , Female , Humans , Immunocompromised Host/physiology , Middle Aged , Mycobacterium avium-intracellulare Infection/microbiology , Mycobacterium avium-intracellulare Infection/pathology
17.
Aust J Gen Pract ; 49(3): 88-92, 2020 03.
Article in English | MEDLINE | ID: mdl-32113206

ABSTRACT

BACKGROUND: The use of potent immunosuppressant medications is becoming more common, particularly the use of biologicals for a range of conditions such as rheumatoid arthritis and inflammatory bowel disease. OBJECTIVE: This article focuses on the implications of immunosuppressant medications for travel, including pre-travel vaccinations, minimising risks during travel and travelling with medicines. DISCUSSION: Pre-travel risk assessment is essential to prepare for safe travel. Live vaccines are contraindicated in people with significant immunosuppression because of the higher risk of adverse events and vaccine-associated disease. Inactivated vaccines can be used but may be less effective. Assessing the degree of immunocompromise in patients taking immunosuppressants includes considering both the medications and the underlying conditions. An individualised approach, often involving expert input, is needed to provide pre-travel health advice and immunisation. Planning ahead for travel is needed to minimise risks.


Subject(s)
Immunocompromised Host/drug effects , Immunosuppressive Agents/adverse effects , Travel , Humans , Immunocompromised Host/physiology , Immunosuppressive Agents/therapeutic use , Vaccination/methods
18.
Am J Emerg Med ; 38(6): 1298.e1-1298.e3, 2020 06.
Article in English | MEDLINE | ID: mdl-32081551

ABSTRACT

Bacterial meningitis is a life-threatening condition that should be addressed as an emergency. The typical culprit microorganisms are targeted empirically with ceftriaxone and vancomycin, in the absence of an immunocompromised state. In this case report, however, we are describing a case of meningitis secondary to Weissella confusa, bacteria inherently resistant to the two drugs commonly used to empirically treat meningitis. Weissella spp. are Gram-positive, catalase-negative coccobacilli and an infrequent cause of infection in humans. Bacteremia followed by endocarditis are the typical clinical manifestations of W. confusa in humans. Other reported manifestations include post-operative osteomyelitis, thumb abscess, infected prosthetic joint, infected peritoneal fluid and peritonitis. To our knowledge, this is the first case of meningitis due to Weissella confusa in the literature. Therefore, we conclude that the isolation of Gram-positive coccobacilli resistant to vancomycin, especially in an immunocompromised host, should raise the suspicion of W. confusa.


Subject(s)
Meningitis, Bacterial/microbiology , Aged , Anti-Bacterial Agents/therapeutic use , Fever/etiology , Humans , Immunocompromised Host/drug effects , Immunocompromised Host/physiology , Male , Meningitis, Bacterial/drug therapy , Microbial Sensitivity Tests/methods , Spinal Puncture/methods , Weissella/drug effects , Weissella/isolation & purification , Weissella/pathogenicity
20.
Neuro Endocrinol Lett ; 40(2): 79-84, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31785214

ABSTRACT

BACKGROUND: The aim of the study was to determine clinical manifestations and outcome of Listeria monocytogenes meningitis (LM) and to compare with other forms of bacterial meningitis (BM). MATERIAL AND METHODS: We analyzed records of all adult patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. RESULTS: Out of 343 analyzed patients with BM 24 were diagnosed to have LM. Patients with LM were older compared to patients with other forms of BM (62 years vs. 57 years, p=0.039), were more likely to have cancer (16.7% vs. 4.7%, p=0.045), receive immunosuppressive treatment (45.8% vs. 10.7%, p<0.001), or be immunocompromised in any way (62.5% vs. 35.5%, p=0.016). Blood tests showed lower WBC (10.7 × 103 cells/µl vs. 15.5 × 103 cells/µl, p=0.004), C-reactive protein (150 mg/L vs. 221 mg/L, p=0,019) and procalcitonin (1.27 ng/mL vs. 3.78 ng/mL, p=0.003) in LM group. Analysis of cerebrospinal fluid showed lower cell count (531.5 cells/µL vs. 1100 cells/µL, p<0.001) and lower chloride (113 mmol/L vs. 117 mmol/L, p=0.036) in patients with LM. In the multiple logistic regression analysis, immunosuppressive therapy was the only variable independently associated with LM (OR:8.72, CI 95%:1.41-64.34, p=0.024). CONCLUSIONS: LM is associated with older age, cancer and immunosuppressive therapy. However, in multivariate analysis only immunosuppressive therapy turned out to be an independent risk factor for LM.


Subject(s)
Listeria monocytogenes/physiology , Meningitis, Listeria/diagnosis , Meningitis, Listeria/pathology , Adult , Aged , Disease Progression , Female , Humans , Immunocompromised Host/physiology , Immunosuppressive Agents/therapeutic use , Listeria monocytogenes/isolation & purification , Male , Meningitis, Listeria/epidemiology , Meningitis, Listeria/etiology , Middle Aged , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/microbiology , Poland/epidemiology , Prognosis , Retrospective Studies , Risk Factors
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