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Respiratory Research Feb 2024Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%....
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 Trem2 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 Trem2 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.
Topics: Animals; Mice; Immunity; Inflammation; Lung; Macrophages; Membrane Glycoproteins; Pneumonia, Pneumocystis; Receptors, Immunologic
PubMed: 38317180
DOI: 10.1186/s12931-024-02709-1 -
Intestinal Research Feb 2024A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by...
BACKGROUND/AIMS
A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30-40 mg). This may relate to physician's concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses.
METHODS
This retrospective cohort study used the Japan Medical Data Center claims database (2012-2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose < 30 mg), guideline-recommended (30-40 mg), and higher groups ( > 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort.
RESULTS
After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization.
CONCLUSIONS
The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.
PubMed: 38311715
DOI: 10.5217/ir.2023.00071 -
Acute and Critical Care Feb 2024In this study, we reviewed the outcomes of pediatric patients with malignancies who underwent hematopoietic stem cell transplantation (HSCT) and extracorporeal membrane...
BACKGROUND
In this study, we reviewed the outcomes of pediatric patients with malignancies who underwent hematopoietic stem cell transplantation (HSCT) and extracorporeal membrane oxygenation (ECMO).
METHODS
We retrospectively analyzed the records of pediatric hemato-oncology patients treated with chemotherapy or HSCT and who received ECMO in the pediatric intensive care unit (PICU) at Seoul National University Children's Hospital from January 2012 to December 2020.
RESULTS
Over a 9-year period, 21 patients (14 males and 7 females) received ECMO at a single pediatric institute; 10 patients (48%) received veno-arterial (VA) ECMO for septic shock (n=5), acute respiratory distress syndrome (ARDS) (n=3), stress-induced myopathy (n=1), or hepatopulmonary syndrome (n=1); and 11 patients (52%) received veno-venous (VV) ECMO for ARDS due to pneumocystis pneumonia (n=1), air leak (n=3), influenza (n=1), pulmonary hemorrhage (n=1), or unknown etiology (n=5). All patients received chemotherapy; 9 received anthracycline drugs and 14 (67%) underwent HSCT. Thirteen patients (62%) were diagnosed with malignancies and 8 (38%) were diagnosed with non-malignant disease. Among the 21 patients, 6 (29%) survived ECMO in the PICU and 5 (24%) survived to hospital discharge. Among patients treated for septic shock, 3 of 5 patients (60%) who underwent ECMO and 5 of 10 patients (50%) who underwent VA ECMO survived. However, all the patients who underwent VA ECMO or VV ECMO for ARDS died.
CONCLUSIONS
ECMO is a feasible treatment option for respiratory or heart failure in pediatric patients receiving chemotherapy or undergoing HSCT.
PubMed: 38303580
DOI: 10.4266/acc.2023.01088 -
AIDS Research and Therapy Jan 2024Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART.
BACKGROUND
Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART.
METHODS
All 0-14-year-old CLHIV admitted to the Ganzhou Center for Disease Control and Prevention from January 2006 to June 2023 were included retrospectively. The information of treatment regimens, disease progression, and laboratory tests of the patients under ART were used to explore the outcomes and impacts of long-term ART. The normality of all the data was tested by the Shapiro-Wilk test.
RESULTS
From 2006 to 2023, 18 CLHIV were reported in Ganzhou. Among them, 11 received ART and were followed up for 60.0 ± 48.4 months. After receiving ART, the median viral load of them decreased from 89,600 copies/ml to 22 copies/ml (P = 0.007), the median CD4 T cell count increased from 380.7 cells/µL to 661.9 cells/µL (P = 0.028), and the median CD8 T cell count decreased from 1065.8 cells/µL to 983.3 cells/µL (P = 0.584). The laboratory test results regarding liver function, renal function, blood cell count, and glucolipid metabolism tended to be within normal reference ranges, and the mean height-for-age z-score and weight-for-age z-score increased. However, all the three CLHIV who received cotrimoxazole developed pneumocystis carinii pneumonia, upper respiratory infection, skin lesions, bacterial pneumonia and/or thrush; the mean body-mass-index-for-age z-score decreased from 0.52 to -0.63.
CONCLUSION
For CLHIV, ART could effectively inhibit the replication of HIV and improve the immune function of patients. More studies that focus on ART in CLHIV are urgently needed.
Topics: Child; Humans; Infant, Newborn; Infant; Child, Preschool; Adolescent; HIV Infections; Retrospective Studies; Anti-Retroviral Agents; Disease Progression; CD4 Lymphocyte Count; China; Viral Load; Anti-HIV Agents
PubMed: 38297382
DOI: 10.1186/s12981-024-00594-8 -
BMC Infectious Diseases Jan 2024Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of...
A regimen based on the combination of trimethoprim/sulfamethoxazole with caspofungin and corticosteroids as a first-line therapy for patients with severe non-HIV-related pneumocystis jirovecii pneumonia: a retrospective study in a tertiary hospital.
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients.
METHODS
We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi'an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15-20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40-80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15-20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups.
RESULTS
The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group.
CONCLUSIONS
Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.
Topics: Humans; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Caspofungin; Retrospective Studies; Tertiary Care Centers; Pneumocystis carinii; Adrenal Cortex Hormones
PubMed: 38297200
DOI: 10.1186/s12879-024-09031-7 -
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 -
Cureus Dec 2023We describe the case of a 36-year-old man diagnosed with human immunodeficiency virus (HIV) following prolonged severe acute respiratory syndrome coronavirus 2...
We describe the case of a 36-year-old man diagnosed with human immunodeficiency virus (HIV) following prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. The patient had a complication of pneumocystis pneumonia. Upon initiating highly active antiretroviral therapy, we monitored HIV RNA levels, CD4+ T-cell count, SARS-CoV-2 viral load, and IgG antibodies against SARS-CoV-2. At 167 days post SARS-CoV-2 diagnosis, the patient's CD4+ T-cell count increased to 180 cells/μL. IgG antibodies against SARS-CoV-2 were undetectable despite a decreased SARS-CoV-2 viral load. HIV screening is necessary in cases of prolonged SARS-CoV-2 pneumonia or persistent SARS-CoV-2 shedding. When diagnosed with HIV infection, it is advisable to consider the possibility of pneumocystis pneumonia.
PubMed: 38283513
DOI: 10.7759/cureus.51189 -
Open Forum Infectious Diseases Jan 2024pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and...
BACKGROUND
pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and guidelines on appropriate prophylaxis are lacking.
METHODS
In this multicenter retrospective trial, all non-HIV adult cases admitted to hospitals in Québec City, Canada, between January 2011 and January 2021 with a diagnosis of PJP were assessed for eligibility.
RESULTS
An overall 129 cases of PJP were included. More than two-thirds had an underlying hematologic disease or an autoimmune/inflammatory condition. Prior to diagnosis, 83.7% were taking corticosteroids, 71.3% immunosuppressive agents (alone or in combination with corticosteroids), and 62% both. A diagnosis of PJP was noted in 22 patients receiving corticosteroids for treatment <28 days. Two patients developed PJP while undergoing corticosteroid monotherapy at a mean daily prednisone-equivalent dose <20 mg/d; 4.7% of our cohort received a PJP prophylaxis. Current recommendations or accepted clinical practices for PJP prophylaxis would not have applied to 48.8% of our patients.
CONCLUSIONS
The use of corticosteroids-in monotherapy or in coadministration with other immunosuppressive agents-remains the principal risk factor for PJP in the non-HIV population. Current prophylaxis guidelines and accepted practices are insufficient to adequately prevent PJP and need to be broadened and updated.
PubMed: 38274551
DOI: 10.1093/ofid/ofad639 -
Frontiers in Cellular and Infection... 2023Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient...
INTRODUCTION
Pneumonia are the leading cause of death worldwide, and antibiotic treatment remains fundamental. However, conventional sputum smears or cultures are still inefficient for obtaining pathogenic microorganisms.Metagenomic next-generation sequencing (mNGS) has shown great value in nucleic acid detection, however, the NGS results for lower respiratory tract microorganisms are still poorly studied.
METHODS
This study dealt with investigating the efficacy of mNGS in detecting pathogens in the lower respiratory tract of patients with pulmonary infections. A total of 112 patients admitted at the First Affiliated Hospital of Zhengzhou University between April 30, 2018, and June 30, 2020, were enrolled in this retrospective study. The bronchoalveolar lavage fluid (BALF) was obtained from lower respiratory tract from each patient. Routine methods (bacterial smear and culture) and mNGS were employed for the identification of pathogenic microorganisms in BALF.
RESULTS
The average patient age was 53.0 years, with 94.6% (106/112) obtaining pathogenic microorganism results. The total mNGS detection rate of pathogenic microorganisms significantly surpassed conventional methods (93.7% vs. 32.1%, P < 0.05). Notably, 75% of patients (84/112) were found to have bacteria by mNGS, but only 28.6% (32/112) were found to have bacteria by conventional approaches. The most commonly detected bacteria included (19.6%), (17.9%), (14.3%), (12.5%), (12.5%), and (11.6%). In 29.5% (33/112) of patients, fungi were identified using mNGS, including 23 cases of (20.5%), 18 of (16.1%), and 10 of (8.9%). However, only 7.1 % (8/112) of individuals were found to have fungi when conventional procedures were used. The mNGS detection rate of viruses was significantly higher than the conventional method rate (43.8% vs. 0.9%, P < 0.05). The most commonly detected viruses included Epstein-Barr virus (15.2%), cytomegalovirus (13.4%), circovirus (8.9%), human coronavirus (4.5%), and rhinovirus (4.5%). Only 29.4% (33/112) of patients were positive, whereas 5.4% (6/112) of patients were negative for both detection methods as shown by Kappa analysis, indicating poor consistency between the two methods (P = 0.340; Kappa analysis).
CONCLUSION
Significant benefits of mNGS have been shown in the detection of pathogenic microorganisms in patients with pulmonary infection. For those with suboptimal therapeutic responses, mNGS can provide an etiological basis, aiding in precise anti-infective treatment.
Topics: Humans; Middle Aged; Retrospective Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Pneumonia; High-Throughput Nucleotide Sequencing; Respiratory System
PubMed: 38264726
DOI: 10.3389/fcimb.2023.1291980 -
Infection and Drug Resistance 2024Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported...
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an acute, rare and potentially fatal drug reaction. To date, limited studies have reported secondary pneumonia (PJP) infection during the treatment of DRESS syndrome. A 53-year-old man was admitted to the hospital due to a persistent fever lasting for 5 days. He had a medical history of hypertension, psoriasis, urticaria, and had recently been treated with carbamazepine for nerve spasm two weeks ago. After admission, the patient presented with a high fever accompanied by chills, abdominal pain, bilateral upper limb muscle pain, and generalized lymph nodes enlargement. Laboratory tests revealed elevated eosinophils and atypical lymphocytes. Subsequently, the patient developed multiple internal organ complications, including oliguria, elevated serum creatinine, liver enzymes, and cardiac troponin I. Based on diagnostic criteria, the patient was diagnosed with DRESS syndrome. To manage the DRESS syndrome, the patient was successively or simultaneously prescribed methylprednisolone, cyclosporin and intravenous immunoglobulin, resulting in an improvement of the condition. However, during the treatment, the patient was infected with . Despite targeted therapy with trimethoprim/sulfamethoxazole, primaquine and clindamycin successively, no remission was observed. Chest CT scans exhibited multiple exudations in both lungs, indicative of interstitial pneumonia. Unfortunately, the patient's oxygenation progressively declined, leading to his untimely demise. This rare case further highlights the need for clinicians to be aware of the risk of infection in DRESS syndrome patients treated with long-term and high-dose glucocorticoid therapy.
PubMed: 38250337
DOI: 10.2147/IDR.S447694