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3.
Artigo em Inglês | MEDLINE | ID: mdl-38511807

RESUMO

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.


Assuntos
Acidose , Hiperpotassemia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/induzido quimicamente , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/complicações , Hiperpotassemia/tratamento farmacológico , Acidose/induzido quimicamente , Acidose/complicações , Acidose/tratamento farmacológico , Rim , Estudos Retrospectivos
4.
Zhonghua Xue Ye Xue Za Zhi ; 45(1): 62-67, 2024 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-38527840

RESUMO

Objectives: To investigate the value of metagenomic next-generation sequencing (mNGS) in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The data of 98 patients with suspected pulmonary infection after allo-HSCT who underwent pathogen detection from bronchoalveolar lavage fluid between June 2016 and August 2023 at Nanfang Hospital were analyzed. The diagnostic performance of mNGS, conventional methods, and real-time quantitative polymerase chain reaction (qPCR) for PJP were compared. Results: A total of 12 patients were diagnosed with PJP, including 11 with a proven diagnosis and 1 with a probable diagnosis. Among the patients with a proven diagnosis, 1 was positive by both conventional methods and qPCR, and 10 were positive by qPCR only. Pneumocystis jirovecii was detected by mNGS in all 12 patients. The diagnostic sensitivity of mNGS for PJP was 100%, which was greater than that of conventional methods (8.3%, P=0.001) and similar to that of qPCR (91.6%, P=1.000) . A total of 75% of the patients developed mixed pulmonary infections, and cytomegalovirus and Epstein-Barr virus were the most common pathogens. Mixed infection was detected in eight patients by mNGS and in five patients by qPCR, but not by conventional methods (P=0.008) . Conclusions: mNGS had good sensitivity for diagnosing PJP after allo-HSCT and was advantageous for detecting mixed infectious pathogens; therefore, mNGS might be an effective supplement to regular detection methods and qPCR.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Pneumonia por Pneumocystis , Pneumonia , Humanos , Pneumonia por Pneumocystis/diagnóstico , Herpesvirus Humano 4 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sequenciamento de Nucleotídeos em Larga Escala , Sensibilidade e Especificidade , Estudos Retrospectivos
5.
Int J Mol Sci ; 25(6)2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38542124

RESUMO

Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus Pneumocystis, which is linked to severe COPD in human patients. Recent evidence has demonstrated that Pneumocystis significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by Pneumocystis infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1ß pro-inflammatory pathway during Pneumocystis infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with Pneumocystis exhibited elevated inflammation levels, including a synergistic increase in IL-1ß and Cox-2. Furthermore, protein levels of the IL-1ß-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with Pneumocystis, while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with Pneumocystis compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with Pneumocystis compared with the other experimental animal groups and correlated with the increase of Tgfß1 mRNA levels. These findings emphasize the role of Pneumocystis as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.


Assuntos
Asma , Pneumocystis , Pneumonia por Pneumocystis , Doença Pulmonar Obstrutiva Crônica , Humanos , Ratos , Animais , Elastase Pancreática/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pulmão/patologia , Asma/metabolismo , Muco/metabolismo , Inflamação/metabolismo , Colágeno/metabolismo
6.
J Clin Microbiol ; 62(4): e0004524, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38477535

RESUMO

Pneumocystis jirovecii pneumonia (PJP) is a serious and sometimes fatal infection occurring in immunocompromised individuals. High-risk patients include those with low CD4 counts due to human immunodeficiency virus infection and transplant recipients. The incidence of PJP is increasing, and rapid detection of PJP is needed to effectively target treatment and improve patient outcomes. A common method used is an immunofluorescent assay (IFA), which has limitations, including labor costs, low sensitivity, and requirement for expert interpretation. This study evaluates the performance of the DiaSorin Molecular Pneumocystis jirovecii analyte-specific reagent (ASR) in a laboratory-developed test (LDT) for the direct detection of P. jirovecii DNA without prior nucleic acid extraction. Respiratory samples (n = 135) previously tested by IFA from 111 patients were included. Using a composite standard of in-house IFA and reference lab PJP PCR, the percent positive agreement for the LDT using the DiaSorin ASR was 97.8% (90/92). The negative percent agreement was 97.7% (42/43). The lower limit of detection of the assay was determined to be 1,200 copies/mL in bronchoalveolar lavage fluid. Analytical specificity was assessed using cultures of oropharyngeal flora and common respiratory bacterial and fungal pathogens. No cross-reactivity was observed. Our study suggests that the DiaSorin Pneumocystis ASR accurately detects P. jirovecii DNA and demonstrates improved sensitivity compared to the IFA method. IMPORTANCE: Our study is unique compared to other previously published studies on the DiaSorin analyte-specific reagent (ASR) because we focused on microbiological diagnostic methods commonly used (immunofluorescent assay) as opposed to pathology findings or reference PCR. In addition, in our materials and methods, we describe the protocol for the use of the DiaSorin ASR as a singleplex assay, which will allow other users to evaluate the ASR for clinical use in their lab.


Assuntos
Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumocystis carinii/genética , Indicadores e Reagentes , Sensibilidade e Especificidade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Hospedeiro Imunocomprometido , DNA
8.
Fam Med Community Health ; 12(1)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485284

RESUMO

INTRODUCTION: Pelvic floor disorders (PFDs) pose substantial physical and psychological burdens for a growing number of women. Given the ubiquity of these conditions and known patient reluctance to seek care, primary care providers (PCPs) have a unique opportunity to increase treatment and provide appropriate referrals for these patients. METHODS: An online survey was administered to PCPs to assess provider practices, knowledge, comfort managing and ease of referral for PFDs. Logistic regression was used to assess the association between demographic/practice characteristics of PCPs and two primary outcomes of interest: discomfort with management and difficulty with referral of PFDs. RESULTS: Of the 153 respondents to the survey, more felt comfortable managing stress urinary incontinence (SUI) and overactive bladder (OAB), compared with pelvic organ prolapse (POP) and faecal incontinence (FI) and were less likely to refer patients with urinary symptoms. Few providers elicited symptoms for POP and FI as compared with SUI and OAB. Provider variables that were significantly associated with discomfort with management varied by PFD, but tended to correlate with less exposure to PFDs (eg, those with fewer years of practice, and internal medicine and family physicians as compared with geriatricians); whereas the factors that were significantly associated with difficulty in referral, again varied by PFD, but were related to practice characteristics (eg, specialist network, type of practice, practice setting and quantity of patients). CONCLUSION: These findings highlight the need to increase PCPs awareness of PFDs and develop effective standardised screening protocols, as well as collaboration with pelvic floor specialists to improve screening, treatment and referral for patients with PFDs.


Assuntos
Incontinência Fecal , Distúrbios do Assoalho Pélvico , Pneumonia por Pneumocystis , Bexiga Urinária Hiperativa , Incontinência Urinária por Estresse , Humanos , Feminino , Distúrbios do Assoalho Pélvico/diagnóstico , Distúrbios do Assoalho Pélvico/terapia , Distúrbios do Assoalho Pélvico/complicações , Estudos Transversais , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/complicações , Incontinência Urinária por Estresse/diagnóstico , Incontinência Urinária por Estresse/terapia , Incontinência Urinária por Estresse/complicações , Pneumonia por Pneumocystis/complicações , Incontinência Fecal/diagnóstico , Incontinência Fecal/terapia , Incontinência Fecal/complicações , Atenção Primária à Saúde
9.
Respir Res ; 25(1): 125, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486264

RESUMO

BACKGROUND: Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. METHODS: In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. RESULTS: BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. CONCLUSIONS: This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.


Assuntos
Microbiota , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/complicações , Transplantados , Linfócitos T CD8-Positivos , Pneumocystis carinii/genética , Pulmão
10.
PLoS One ; 19(3): e0297619, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38526997

RESUMO

The epidemiology of Human Immunodeficiency Virus (HIV)-associated pneumocystosis (HAP) is poorly described on a worldwide scale. We searched related databases between January 2000 and December 2022 for studies reporting HAP. Meta-analysis was performed using StatsDirect (version 2.7.9) and STATA (version 17) according to the random-effects model for DerSimonian and Laird method and metan and metaprop commands, respectively. Twenty-nine studies with 38554 HIV-positive, 79893 HIV-negative, and 4044 HAP populations were included. The pooled prevalence of HAP was 35.4% (95% CI 23.8 to 47.9). In contrast, the pooled prevalence of PCP among HIV-negative patients was 10.16% (95% CI 2 to 25.3). HIV-positive patients are almost 12 times more susceptible to PCP than the HIV-negative population (OR: 11.710; 95% CI: 5.420 to 25.297). The mortality among HAP patients was 52% higher than non-PCP patients (OR 1.522; 95% CI 0.959 to 2.416). HIV-positive men had a 7% higher chance rate for PCP than women (OR 1.073; 95% CI 0.674 to 1.706). Prophylactic (OR: 6.191; 95% CI: 0.945 to 40.545) and antiretroviral therapy (OR 3.356; 95% CI 0.785 to 14.349) were used in HAP patients six and three times more than HIV-positive PCP-negatives, respectively. The control and management strategies should revise and updated by health policy-makers on a worldwide scale. Finally, for better management and understanding of the epidemiology and characteristics of this coinfection, designing further studies is recommended.


Assuntos
Infecções por HIV , Soropositividade para HIV , Pneumonia por Pneumocystis , Masculino , Humanos , Feminino , HIV , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/epidemiologia , Prevalência , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
11.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(3): 207-213, 2024 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-38448169

RESUMO

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia por Pneumocystis , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Prognóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Prednisona , Neoplasias Pulmonares/tratamento farmacológico
12.
Respir Investig ; 62(3): 377-383, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452442

RESUMO

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.


Assuntos
Artrite Reumatoide , Produtos Biológicos , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/complicações , Estudos Retrospectivos , Mortalidade Hospitalar , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos
13.
mBio ; 15(3): e0327723, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38345378

RESUMO

Pneumocystis jirovecii is a major fungal pathogen of humans that causes life-threatening lung infections in immunocompromised individuals. Despite its huge global impact upon human health, our understanding of the pathobiology of this deadly fungus remains extremely limited, largely because it is not yet possible to cultivate Pneumocystis in vitro, independently of the host. However, a recent paper by Munyonho et al. offers a major step forward (F. T. Munyonho, R. D. Clark, D. Lin, M. S. Khatun, et al., 2023, mBio 15:e01464-23, https://doi.org/10.1128/mbio.01464-23). They show that it is possible to maintain both the trophozoite and cyst forms of the mouse pathogen, Pneumocystis murina, in precision-cut lung slices for several weeks. Furthermore, they demonstrate that this offers the exciting opportunity to examine potential virulence factors such as possible biofilm formation as well as antifungal drug responses in the lung.


Assuntos
Pneumocystis , Pneumonia por Pneumocystis , Humanos , Animais , Camundongos , Antifúngicos , Pulmão
14.
Transplant Proc ; 56(2): 453-455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336484

RESUMO

We describe the case of a 51-year-old Caucasian man with a background of a cardiac and renal transplant who developed Enterocytozoon bieneusi colitis and pneumocystis jirovecii (PJP) pneumonia following treatment for suspected rejection. The patient developed methemoglobinemia which was attributed to primaquine. He was treated with intravenous methylene blue leading to clinical and biochemical resolution. We describe in detail the pathophysiological mechanism for methemoglobinemia and its treatment, in particular with methylene blue.


Assuntos
Transplante de Rim , Metemoglobinemia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Metemoglobinemia/complicações , Azul de Metileno , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/complicações , Primaquina/efeitos adversos
15.
J Neurooncol ; 167(1): 211-217, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38363493

RESUMO

PURPOSE: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. METHODS: This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. RESULTS: Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION: These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.


Assuntos
Neoplasias Encefálicas , Neutropenia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/prevenção & controle , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Pentamidina/farmacologia , Pentamidina/uso terapêutico , Estudos Retrospectivos , Temozolomida/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Neoplasias Encefálicas/radioterapia
16.
Respir Res ; 25(1): 72, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317180

RESUMO

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. METHODS: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. RESULTS: Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. CONCLUSION: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.


Assuntos
Glicoproteínas de Membrana , Pneumonia por Pneumocystis , Receptores Imunológicos , Animais , Camundongos , Imunidade , Inflamação/metabolismo , Pulmão/microbiologia , Macrófagos/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Pneumonia por Pneumocystis/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo
17.
Transpl Int ; 37: 12192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328616

RESUMO

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Linfopenia , Pneumocystis carinii , Pneumonia por Pneumocystis , Trombocitopenia , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos de Casos e Controles , Transplante de Rim/efeitos adversos , Creatinina , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Fatores de Risco , Linfopenia/complicações , Trombocitopenia/complicações , Transplantados , Estudos Retrospectivos
18.
PLoS One ; 19(2): e0295570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38421982

RESUMO

Primary care physicians (PCPs) suffered from heavy workloads and health problems during COVID-19 pandemics, and building their confidence in pandemic response has great potential to improve their well-being and work performance. We identified the organizational factors associated with their confidence in pandemic response and proposed potential management levers to guide primary care response for the pandemic. We conducted a cross-sectional survey with 224 PCPs working in 38 community health centers in China. Guided by self-efficacy theory, organization-level factors (organizational structure and organizational culture) and physician-level factors (job skill variety, perceived organizational support, work-family conflict, and professional fulfillment) were selected, and two-level ordinal logit models were built to examine their association with PCPs' confidence in pandemic response. We found that hierarchical culture (OR = 3.51, P<0.05), perceived organizational support (OR = 2.36, P<0.05), job skill variety (OR = 1.86, P<0.05), and professional fulfillment (OR = 2.26, P<0.05) were positively associated with PCPs' confidence in pandemic response. However, the influence of organization structure and work-family conflict seemed limited. The study not only increases our understanding of the influence of organizational context on PCPs' pandemic response confidence, but also points out potential management levers for front-line primary care managers to enhance primary care pandemic response capacity.


Assuntos
Médicos de Atenção Primária , Pneumonia por Pneumocystis , Humanos , Estudos Transversais , Pandemias , Pessoal de Saúde , China/epidemiologia
19.
BMC Prim Care ; 25(1): 74, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418978

RESUMO

BACKGROUND: Physician burnout remains a prevalent issue globally, negatively affecting work satisfaction and patient care. However, exploration of the physical work environments of physicians, a potential influencing factor for burnout, remains scarce. The physical work environment is everything that surrounds the physician, including the doctor's office, the clinic, the clinic's building, the waiting, and staff rooms. The aims of this study were to describe aspects of the physical work environment of primary care physicians (PCPs) and to explore the association between the physical work environment and burnout. METHODS: In this cross-sectional study, we emailed questionnaires to an online community of PCPs in Israel in October 2021. We asked physicians about their satisfaction with their physical work environment, evaluated elements of the work environment, and assessed burnout status (with the Shirom-Melamed Burnout Measure, SMBM). We used the Chi-square and Mann-Witney tests to compare categorical and continuous variables and used logistic regression for the final model. RESULTS: Two hundred twenty-one PCPs answered the questionnaire (27.6% response rate). Over a third (35.7%) of respondents reported high burnout. PCPs who were satisfied with their general physical environment had lower burnout rates than those who were unsatisfied (28.1% vs. 47.8%, p-value < 0.001). We found positive correlations between general satisfaction with the physical work environment and the scores achieved for the doctor's office, the clinic, the clinic's building, and the waiting room. In the multivariate analysis, high satisfaction with the general physical work environment was associated with decreased odds for burnout (OR-0.50, 95% CI 0.25-0.99, p-value-0.048). CONCLUSION: The doctor's office, the clinic, the clinic's building, and the waiting room affected general satisfaction from the physical work environment. High satisfaction with the physical work environment reduced burnout rates. Future studies are needed to determine whether PCPs and managers should invest in the physical work environment to decrease burnout and increase satisfaction.


Assuntos
Esgotamento Profissional , Médicos de Atenção Primária , Pneumonia por Pneumocystis , Humanos , Estudos Transversais , Israel/epidemiologia , Esgotamento Psicológico , Esgotamento Profissional/epidemiologia , Condições de Trabalho
20.
J Med Case Rep ; 18(1): 52, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342895

RESUMO

INTRODUCTION AND IMPORTANCE: Pneumocystis jirovecii (PJP) pneumonia is a serious life-threatening condition in immunocompromised individuals and is often associated with human immunodeficiency virus (HIV) + patients. We describe a case of PJP pneumonia which provided a diagnostic challenge in a patient who presented with no known risk factors leading to a delay in initiation of appropriate antibiotic therapy. CASE PRESENTATION: A 71-year-old previously healthy white/Caucasian male presented with subacute hypoxic respiratory failure due to multifocal pneumonia with diffuse bilateral ground glass opacities with consolidations despite prior treatment with antibiotics and steroids. He was admitted and started on intravenous broad-spectrum antibiotics but continued to deteriorate, eventually requiring intubation and transfer to the ICU. Bronchoscopy revealed PJP and treatment was initiated, but the patient developed refractory shock and multiorgan failure, and ultimately died. It was later discovered that he was HIV-1 positive. CLINICAL DISCUSSION: PJP, as a potential cause of his presentation, was not considered given that our patient lacked any overt risk factors for PJP pneumonia. He continued to worsen despite broad spectrum antibiotic therapy and hence bronchoscopy was pursued. His clinical profile, in hindsight, was suspicious for PJP pneumonia and early PJP-directed antibiotic therapy may have prevented a fatal outcome, as in this case. There was an element of cognitive bias across multiple providers which may have contributed to the delay in treatment despite his rapid clinical decline while on conventional pneumonia treatment protocol. His diagnosis was later evident when his BAL-DFA grew PJP in addition to his low levels of CD4 and CD8 cells. He was found to be HIV-1 positive five days after his death; there was a delay in this diagnosis since all positive HIV tests from the hospital are reported as 'pending' until the presumptive positive sample goes to the Connecticut Department of Public Health State laboratory for the confirmatory test. PJP-targeted therapies were initiated later in our patient's hospital course when the infection had progressed to refractory septic shock with multiorgan failure and eventual death. CONCLUSION: PJP pneumonia is a fatal disease if not recognized early in the course of illness, and the patient usually undergoes multiple antibiotic regimens before they are diagnosed and receive appropriate clinical care. The gold standard of diagnostic testing for PJP is by obtaining bronchial washings through a flexible bronchoscopy and the turnaround time for such results may take a few days to result. A significant proportion of patients may not have any overt risk factors of immunosuppression and early empiric treatment for PJP may be clinically appropriate as the delay in diagnosis may be associated with significant morbidity and mortality risk.


Assuntos
Infecções por HIV , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Idoso , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Fatores de Risco , Antibacterianos/uso terapêutico , Infecções por HIV/complicações
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