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Cureus Dec 2023Objective To investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall outcomes of pneumonia (PJP) in...
Objective To investigate the predisposing factors, disease course, potential complications, role of primary prophylaxis, and overall outcomes of pneumonia (PJP) in cancer patients. Methods The study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. We analyzed the medical records of cancer patients diagnosed with PJP from January 2018 to December 2022 and collected data about demographic characteristics, clinical presentation, predisposing factors, treatment, complications, and mortality rates. We used SPSS 20 (IBM Corp., Armonk, NY, USA) for data analysis. Results Out of 84 patients, 59.5% (n=50) were males and most of the patients belonged to the age group 41 to 65 years. Sixty-seven point nine percent (67.9%; n=57) of patients had underlying hematological malignancy, including three bone marrow transplant recipients while 32.2% (n=27) of patients had underlying solid organ malignancy. We also observed the use of corticosteroids, rituximab, and fludarabine as predisposing factors in 15% (n=13), 27% (n=23), and 3.7%(n=03) of patients, respectively. The most common symptoms were dyspnea (88%; n=74), followed by fever (69%; n=58) and cough (69%; n=58). The former one was more prevalent in hematological malignancy patients as compared to the solid organ tumor group (p-value 0.001). We noted respiratory failure (45.2%; n=38), ICU stay (52.38%; n=44), death (32%; n=27), and shock (10.7% n=9) as the most common PJP-related complications. Moreover, all these complications were more frequent in hematological malignancy patients. We also observed that only three patients developed PJP while on adequate primary prophylaxis for this condition. The overall all-cause one-month mortality was 32% (n=27). Conclusion Cancer patients, especially those with hematological malignancies presenting with symptoms suggestive of PJP, need careful evaluation and preemptive treatment as PJP-related mortality is higher in cancer patients. Early diagnosis and treatment in this population can be lifesaving. Moreover, all cancer patients should receive PJP prophylaxis when indicated.
PubMed: 38283518
DOI: 10.7759/cureus.51291 -
Journal of Molecular Medicine (Berlin,... Oct 2023The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family... (Review)
Review
The transcription factor GATA2 is involved in human diseases ranging from hematopoietic disorders, to cancer, to infectious diseases. GATA2 is one of six GATA-family transcription factors that act as pioneering transcription factors which facilitate the opening of heterochromatin and the subsequent binding of other transcription factors to induce gene expression from previously inaccessible regions of the genome. Although GATA2 is essential for hematopoiesis and lymphangiogenesis, it is also expressed in other tissues such as the lung, prostate gland, gastrointestinal tract, central nervous system, placenta, fetal liver, and fetal heart. Gene or transcriptional abnormalities of GATA2 causes or predisposes patients to several diseases including the hematological cancers acute myeloid leukemia and acute lymphoblastic leukemia, the primary immunodeficiency MonoMAC syndrome, and to cancers of the lung, prostate, uterus, kidney, breast, gastric tract, and ovaries. Recent data has also linked GATA2 expression and mutations to responses to infectious diseases including SARS-CoV-2 and Pneumocystis carinii pneumonia, and to inflammatory disorders such as atherosclerosis. In this article we review the role of GATA2 in the etiology and progression of these various diseases.
PubMed: 37624387
DOI: 10.1007/s00109-023-02359-8 -
Pathogens (Basel, Switzerland) Oct 2023Post-transplant pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant... (Review)
Review
Post-transplant pneumonia (PcP) is an uncommon but increasingly reported disease among solid organ transplantation (SOT) recipients, associated with significant morbidity and mortality. Although the introduction of PcP prophylaxis has reduced its overall incidence, its prevalence continues to be high, especially during the second year after transplant, the period following prophylaxis discontinuation. We recently described two cases of PcP occurring more than one year after heart transplantation (HT) in patients who were no longer receiving PcP prophylaxis according to the local protocol. In both cases, the disease was diagnosed following the diagnosis of a viral illness, resulting in a significantly increased risk for PcP. While current heart transplantation guidelines recommend prophylaxis for up to 6-12 months after transplantation, after that period they only suggest an extended prophylaxis regimen in high-risk patients. Recent studies have identified several new risk factors that may be linked to an increased risk of PcP infection, including medication regimens and patient characteristics. Similarly, the indication for PcP prophylaxis in non-HIV patients has been expanded in relation to the introduction of new medications and therapeutic regimens for immune-mediated diseases. In our experience, the first patient was successfully treated with non-invasive ventilation, while the second required tracheal intubation, invasive ventilation, and extracorporeal CO2 removal due to severe respiratory failure. The aim of this double case report is to review the current timing of PcP prophylaxis after HT, the specific potential risk factors for PcP after HT, and the determinants of a prompt diagnosis and therapeutic approach in critically ill patients. We will also present a possible proposal for future investigations on indications for long-term prophylaxis.
PubMed: 37887781
DOI: 10.3390/pathogens12101265 -
Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
BMC Infectious Diseases Nov 2023Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to...
OBJECTIVE
Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj.
METHODS
A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed.
RESULTS
Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support.
CONCLUSION
The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; DNA Copy Number Variations; Bronchoalveolar Lavage Fluid; Polymerase Chain Reaction; Pneumocystis; Respiratory Distress Syndrome; Pneumocystis carinii
PubMed: 38012564
DOI: 10.1186/s12879-023-08580-7 -
BMC Infectious Diseases Jul 2023Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation... (Review)
Review
OBJECTIVE
Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for PJP.
METHODS
A comprehensive electronic literature search of Web of Knowledge, PubMed, Cochrane Library, CNKI and Wanfang data was performed. Bivariate analysis was conducted to calculate the pooled sensitivity, specificity, diagnostic odds ratio (DOR), the area under the summary receiver operator characteristic (SROC) curve and the Q-point value (Q*).
RESULTS
The literature search resulted in 9 studies with a total of 1343 patients, including 418 cases diagnosed with PJP and 925 controls. The pooled sensitivity of mNGS for diagnosis of PJP was 0.974 [95% confidence interval (CI), 0.953-0.987]. The pooled specificity was 0.943 (95% CI, 0.926-0.957), the DOR was 431.58 (95% CI, 186.77-997.27), the area under the SROC curve was 0.987, and the Q* was 0.951. The I test indicated no heterogeneity between studies. The Deek funnel test suggested no potential publication bias. Subgroup analyses showed that the area under the SROC curve of mNGS for diagnosis of PJP in immunocompromised and non-HIV patients was 0.9852 and 0.979, respectively.
CONCLUSIONS
Current evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of PJP. The mNGS is a promising tool for assessment of PJP in both immunocompromised and non-HIV patients.
Topics: Humans; Correlation of Data; High-Throughput Nucleotide Sequencing; Immunocompromised Host; Knowledge; Pneumonia, Pneumocystis
PubMed: 37430211
DOI: 10.1186/s12879-023-08440-4 -
Frontiers in Allergy 2023Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory... (Review)
Review
Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory biomarkers present in the airways to further understand the pathophysiology of different inflammatory respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) as well as the diagnosis of lung diseases such as lung cancer, tuberculosis, and pneumonia. It is a non-invasive, safe, cost-effective, and reliable technique reported to exhibit a high success rate. However, due to being technically demanding and time-consuming and having the need of employing trained staff, this technique is only used in restricted research centres and in limited centres of clinical use. When the sputum is collected after induction, the primary goal is to obtain a differential cell count and evaluate the molecular biomarkers of airway inflammation such as eosinophil cationic protein, eosinophil-derived neurotoxin, major basic protein, tryptase, cytokine production [e.g., interleukin (IL)-5], albumin, and fibrinogen. In addition, cytospins from the processed sputum are used for immunocytochemical staining of cellular products such as EG-2 reactive protein, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor alpha, and IL-8 that play significant roles in understanding the pathophysiology of inflammatory airway diseases. Nowadays, this technique can be further used by performing an additional analysis such as flow cytometry and hybridisation on the sputum supernatant to investigate more the immune response and pathophysiological process of such various respiratory diseases. In addition, the application of sputum fluid phase to assess the biomarkers could be used more routinely in pathological laboratories for diagnosing lung cancer, COPD, and asthma as well as for monitoring lung cancer progression and asthma and COPD treatment, allowing for early detection and a better treatment provided by the clinicians.
PubMed: 37901763
DOI: 10.3389/falgy.2023.1282782 -
Clinical Microbiology and Infection :... Oct 2023
Topics: Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Clinical Trials as Topic
PubMed: 37179007
DOI: 10.1016/j.cmi.2023.05.004 -
Annals of Medicine Dec 2023To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori...
AIM
To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.
METHODS
52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.
RESULTS
The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS ( < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, = .0013 and = .0015, respectively). Notably, all the blood samples showing positive mNGS for came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus.
CONCLUSIONS
mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.
Topics: Humans; Pneumonia, Pneumocystis; Epstein-Barr Virus Infections; Sensitivity and Specificity; Herpesvirus 4, Human; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 37403381
DOI: 10.1080/07853890.2023.2232358 -
Chest Jun 2024
Topics: Humans; Pneumonia, Pneumocystis
PubMed: 38852956
DOI: 10.1016/j.chest.2024.02.038