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ELife Apr 2024Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of...
Anticancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16 T cell population, with the highest CD16 T proportion in a fatal case. In ICI-ILD, we found an increase in CD57 CD8 T cells expressing immune checkpoints (TIGIT LAG3 TIM-3 PD-1), FCRL5 B cells, and CCR2 CCR5 CD14 monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.
Topics: Humans; CD8-Positive T-Lymphocytes; Neoplasms; Pneumonia; B-Lymphocytes; Drug-Related Side Effects and Adverse Reactions; Lung Diseases, Interstitial
PubMed: 38607373
DOI: 10.7554/eLife.87288 -
International Journal of STD & AIDS Apr 2024Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national...
Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician's concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians' decision-making. Introduction of pharmacist-led interventions/alerts using patients' electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite "immune reconstitution".
PubMed: 38606484
DOI: 10.1177/09564624241245155 -
Clinical Infectious Diseases : An... Apr 2024
Review
Topics: Adult; Humans; Glucocorticoids; Opportunistic Infections; Pneumocystis; Pneumonia, Pneumocystis
PubMed: 38598566
DOI: 10.1093/cid/ciae129 -
Microbiology and Molecular Biology... Jun 2024SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to... (Review)
Review
SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with being the only one known to cause disease in humans. The mystery of origin and speciation is just beginning to unravel. Here, we provide a review of the major steps of evolution. The genus likely originated from soil or plant-associated organisms during the period of Cretaceous ~165 million years ago and successfully shifted to mammals. The transition coincided with a substantial loss of genes, many of which are related to the synthesis of nutrients that can be scavenged from hosts or cell wall components that could be targeted by the mammalian immune system. Following the transition, the genus cospeciated with mammals. Each species specialized at infecting its own host. Host specialization is presumably built at least partially upon surface glycoproteins, whose protogene was acquired prior to the genus formation. appeared at ~65 million years ago, overlapping with the emergence of the first primates. and its sister species , which infects macaques nowadays, may have had overlapping host ranges in the distant past. Clues from molecular clocks suggest that did not cospeciate with humans. Molecular evidence suggests that speciation involved chromosomal rearrangements and the mounting of genetic barriers that inhibit gene flow among species.
Topics: Humans; Animals; Pneumocystis carinii; Phylogeny; Pneumocystis Infections; Pneumocystis; Evolution, Molecular; Host Specificity; Pneumonia, Pneumocystis; Genome, Fungal; Mammals; Biological Evolution
PubMed: 38587383
DOI: 10.1128/mmbr.00202-22 -
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 -
Pneumonia (Nathan Qld.) Apr 2024Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no...
Leprosy reactions often require prolonged high-dose steroids or immunosuppressive drugs, putting patients at risk of Pneumocystis jirovecii pneumonia (PJP). However, no PJP cases are reported, possibly due to dapsone treatment for leprosy. In patients with leprosy reactions not receiving dapsone because of toxicity or resistance and requiring long-term immunosuppression, PJP prophylaxis should be considered.
PubMed: 38576014
DOI: 10.1186/s41479-024-00127-x -
Monaldi Archives For Chest Disease =... Apr 2024In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in...
In this study, we compared the predisposing factors, key demographic and clinical characteristics, clinical outcomes, and factors associated with poor prognosis in pneumocystis pneumonia (PCP) infection among the human immunodeficiency virus (HIV)-positive and non-HIV patient populations. This retrospective analysis was conducted at the Aga Khan University Hospital, Karachi, via the collection and analysis of patient records with a diagnosis of "pneumocystosis" between January 2015 and October 2020. Additionally, the laboratory database was evaluated, and patients with a laboratory-confirmed diagnosis of PCP were included. During the study period, 52 laboratory-confirmed hospitalized PCP patients were identified. Of these, 23 and 29 patients were diagnosed using microscopy and polymerase chain reaction, respectively. 34.6% of our patients were HIV positive, with a median CD4 count of 20.5 cells/mm3 (range: 10.7-50.5). Other conditions identified were corticosteroid use, autoimmune diseases, malignancy, radiation, and chemotherapy. On chest imaging, consolidation was found in 30%, ground-glass opacities in 24%, and nodular infiltrates in 20% of the cases. HIV-positive patients had a lower hemoglobin level and a higher level of β-D-glucan at the time of admission, whereas non-HIV patients were found to have more co-morbid conditions than HIV patients. We observed no difference in clinical outcomes between the two populations. Factors associated with a poor prognosis among our patients included concomitant infections at the time of diagnosis, the need for invasive mechanical ventilation, and a longer duration of stay in the hospital as well as the intensive care unit.
PubMed: 38572694
DOI: 10.4081/monaldi.2024.2810 -
International Journal of Clinical... Apr 2024An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). (Review)
Review
BACKGROUND
An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs).
AIM
This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs.
METHOD
We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs.
RESULTS
Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections.
CONCLUSION
This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.
PubMed: 38570474
DOI: 10.1007/s11096-024-01704-2 -
Cleveland Clinic Journal of Medicine Apr 2024
Topics: Humans; Pneumonia, Pneumocystis; Adrenal Cortex Hormones
PubMed: 38561210
DOI: 10.3949/ccjm.91a.23082 -
The Journal of Rheumatology Jun 2024We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk...
OBJECTIVE
We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality.
METHODS
We conducted a retrospective study of youth aged 2 to 21 years using International Classification of Diseases (ICD) codes for SLE assigned during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009 to 2021. Generalized linear mixed effects models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection.
RESULTS
We identified 8588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion that increased over time ( = 0.04). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n = 103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n = 60). The highest mortality rates occurred with pneumonia (21%) and other fungal infections (21%). Lupus nephritis (LN) and endstage renal disease (ESRD) were associated with increased odds of ICU admission (odds ratio [OR] 1.47 [95% CI 1.2-1.8] and OR 2.40 [95% CI 1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality (OR 2.34 [95% CI 1.1-4.9]).
CONCLUSION
Hospitalizations with ICD codes for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. LN and ESRD were risk factors for poor outcomes.
PubMed: 38561187
DOI: 10.3899/jrheum.2023-1219