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Journal of Translational Medicine Jun 2024The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients.
METHODS
We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis.
RESULTS
A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation.
CONCLUSION
This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.
Topics: Humans; COVID-19; Mesenchymal Stem Cell Transplantation; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Mesenchymal Stem Cells
PubMed: 38851730
DOI: 10.1186/s12967-024-05358-6 -
Frontiers in Cellular and Infection... 2024The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of...
BACKGROUND
The microbiota-gut-lung axis has elucidated a potential association between gut microbiota and idiopathic pulmonary fibrosis (IPF). However, there is a paucity of population-level studies with providing robust evidence for establishing causality. This two-sample Mendelian randomization (MR) analysis aimed to investigate the causal relationship between the gut microbiota and IPF as well as lung function.
MATERIALS AND METHODS
Adhering to Mendel's principle of inheritance, this MR analysis utilized summary-level data from respective genome-wide association studies (GWAS) involving 211 gut microbial taxa, IPF, and lung function indicators such as FEV, FVC, and FEV/FVC. A bidirectional two-sample MR design was employed, utilizing multiple MR analysis methods, including inverse variance-weighted (IVW), weighted median, MR-Egger, and weighted mode. Multivariable MR (MVMR) was used to uncover mediating factors connecting the exposure and outcome. Additionally, comprehensive sensitivity analyses were conducted to ensure the robustness of the results.
RESULTS
The MR results confirmed four taxa were found causally associated with the risk of IPF. (OR=0.773, 95% CI: 0.610-0.979, p=0.033), (OR=0.773, 95% CI: 0.610-0.979, p=0.033), and (OR=0.793, 95% CI: 0.652-0.965, p=0.020) exerted protective effects on IPF, while (OR=1.349, 95% CI: 1.021-1.783, p=0.035) promote the development of IPF. Several taxa were causally associated with lung function, with those in , and being the most prominent beneficial microbiota, while those in , and were associated with impaired lung function. As for the reverse analysis, MR results confirmed the effects of FEV and FVC on the increased abundance of six taxa (, and ) with a boosted level of evidence. MVMR suggested monounsaturated fatty acids, total fatty acids, saturated fatty acids, and ratio of omega-6 fatty acids to total fatty acids as potential mediating factors in the genetic association between gut microbiota and IPF.
CONCLUSION
The current study suggested the casual effects of the specific gut microbes on the risk of IPF and lung function. In turn, lung function also exerted a positive role in some gut microbes. A reasonable dietary intake of lipid substances has a certain protective effect against the occurrence and progression of IPF. This study provides novel insights into the potential role of gut microbiota in IPF and indicates a possible gut microbiota-mediated mechanism for the prevention of IPF.
Topics: Humans; Mendelian Randomization Analysis; Idiopathic Pulmonary Fibrosis; Gastrointestinal Microbiome; Genome-Wide Association Study; Lung; Respiratory Function Tests; Genetic Predisposition to Disease
PubMed: 38841114
DOI: 10.3389/fcimb.2024.1348685 -
Virology Journal Jun 2024Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality.
METHODS
A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation.
RESULTS
A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death CONCLUSIONS: Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.
Topics: Humans; Hospitalization; Immunocompromised Host; HIV Infections; CD4 Lymphocyte Count; Mpox (monkeypox); Disease Outbreaks; Immunosuppression Therapy; Viral Load
PubMed: 38840177
DOI: 10.1186/s12985-024-02392-0 -
Scientific Reports Jun 2024Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care, but the efficacy for... (Meta-Analysis)
Meta-Analysis
Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care, but the efficacy for mortality prediction of tools like PSI, A-DROP, I-ROAD, and CURB-65, widely used for predicting mortality in community-acquired and hospital-acquired pneumonia cases, remains controversial. In this study, we conducted a systematic review and meta-analysis using PubMed, Cochrane Library (trials), and Ichushi web database (accessed on August 22, 2022). We identified articles evaluating either PSI, A-DROP, I-ROAD, or CURB-65 and the mortality outcome in patients with HCAP, and calculated the pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the summary area under the curves (AUCs) for mortality prediction. Additionally, the differences in predicting prognosis among these four assessment tools were evaluated using overall AUCs pooled from AUC values reported in included studies. Eventually, 21 articles were included and these quality assessments were evaluated by QUADAS-2. Using a cut-off value of moderate in patients with HCAP, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were found to be 0.91-0.97, 0.15-0.44, 1.14-1.66, 0.18-0.33, and 3.86-9.32, respectively. Upon using a cut-off value of severe in those patients, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were 0.63-0.70, 0.54-0.66, 1.50-2.03, 0.47-0.58, and 2.66-4.32, respectively. Overall AUCs were 0.70 (0.68-0.72), 0.70 (0.63-0.76), 0.68 (0.64-0.73), and 0.67 (0.63-0.71), respectively, for PSI, A-DROP, I-ROAD, and CURB-65 (p = 0.66). In conclusion, these severity assessment tools do not have enough ability to predict mortality in HCAP patients. Furthermore, there are no significant differences in predictive performance among these four severity assessment tools.
Topics: Humans; Healthcare-Associated Pneumonia; Severity of Illness Index; Prognosis; Area Under Curve
PubMed: 38839837
DOI: 10.1038/s41598-024-63618-3 -
Therapeutic Advances in Infectious... 2024, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called... (Review)
Review
BACKGROUND
, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of , and risk factors, mortality rate, and underlying condition associated with aspergillosis.
METHODS
Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis.
RESULTS
was prominently reported ( = 2679, 75.14%), followed by ( = 437, 12.25%), ( = 219, 6.14%), and ( = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases ( = 1956) and possible cases ( = 341). In patients, cough emerged as the most common complaint ( = 1819, 18.54%), followed by asthma ( = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing ( = 12, 25.53%), Guangdong ( = 7, 14.89%), and Shanghai ( = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency ( = 8, 7.92%), Guangdong recorded a relatively high number ( = 3, 37.5%), followed by Beijing ( = 2, 25.0%), and Shanghai ( = 1, 12.5%). Percentage of death reported: IPA had the highest rate ( = 447, 68.87%), followed by CPA ( = 181, 27.88%) and ABPA ( = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease ( = 3765, 60.53%), previous tuberculosis ( = 416, 6.68%), and organ transplant or organ failure ( = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy ( = 622, 10.0%).
CONCLUSION
This review sheds light on the prevalence patterns of species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies.
REGISTRATION
This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.
PubMed: 38835831
DOI: 10.1177/20499361241252537 -
Respiratory Medicine 2024Anxiety is common in those with chronic physical health conditions and can have significant impacts on both quality of life and physical health outcomes. Despite this,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Anxiety is common in those with chronic physical health conditions and can have significant impacts on both quality of life and physical health outcomes. Despite this, there are limited studies comprehensively investigating the prevalence of anxiety in respiratory and sleep medicine settings. This systematic review and meta-analysis aims to provide insight into the global prevalence of anxiety symptoms/disorders in respiratory and sleep medicine outpatients.
METHODS
PubMed, Embase, Cochrane, PsycINFO and Google Scholar databases were searched from database inception to January 23, 2023 for studies assessing the prevalence of anxiety in adult (≥16 years) respiratory and sleep medicine outpatients. Data was screened and extracted independently by two investigators. Anxiety was measured using various self-report questionnaires, structured interviews, and/or patient records. Using CMA software for the meta-analysis, a random-effects model was used for pooled estimates, and subgroup analysis was conducted on relevant models using a mixed-effects model.
RESULTS
116 studies were included, featuring 36,340 participants across 40 countries. The pooled prevalence of anxiety was 30.3 % (95%CI 27.9-32.9 %, 10,679/36,340). Subgroup analysis found a significant difference across type of condition, with pulmonary tuberculosis the highest at 43.1 % and COVID-19 outpatients the lowest at 23.4 %. No significant difference was found across anxiety types, country or age. Female sex and the use of self-report measures was associated with significantly higher anxiety estimates.
CONCLUSIONS
Anxiety is a common experience amongst patients in respiratory and sleep medicine outpatient settings. Thus, it is crucial that anxiety identification and management is considered by physicians in the field.
REGISTRATION
The protocol is registered in PROSPERO (CRD42021282416).
Topics: Humans; Prevalence; Anxiety; Sleep Wake Disorders; COVID-19; Female; Male; Adult; Respiratory Tract Diseases; Quality of Life
PubMed: 38823565
DOI: 10.1016/j.rmed.2024.107677 -
Frontiers in Public Health 2024The timely diagnosis of tuberculosis through innovative biomarkers that do not rely on sputum samples is a primary focus for strategies aimed at eradicating... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The timely diagnosis of tuberculosis through innovative biomarkers that do not rely on sputum samples is a primary focus for strategies aimed at eradicating tuberculosis. miR-29 is an important regulator of tuberculosis pathogenesis. Its differential expression pattern in healthy, latent, and active people who develop tuberculosis has revealed its potential as a biomarker in recent studies. Therefore, a systematic review and meta-analysis were performed for the role of miR-29 in the diagnosis of tuberculosis.
METHODS
EMBASE, PubMed, CNKI, Web of Science, and Cochrane Library databases were searched utilizing predefined keywords for literature published from 2000 to February 2024.Included in the analysis were studies reporting on the accuracy of miR-29 in the diagnosis of tuberculosis, while articles assessing other small RNAs were not considered. All types of study designs, including case-control, cross-sectional, and cohort studies, were included, whether prospectively or retrospectively sampled, and the quality of included studies was determined utilizing the QUADAS-2 tool. Publication bias was analyzed via the construction of funnel plots. Heterogeneity among studies and summary results for specificity, sensitivity, and diagnostic odds ratio (DOR) are depicted in forest plots.
RESULTS
A total of 227 studies were acquired from the various databases, and 18 articles were selected for quantitative analysis. These articles encompassed a total of 2,825 subjects, primarily sourced from the Asian region. Patient specimens, including sputum, peripheral blood mononuclear cells, cerebrospinal fluid and serum/plasma samples, were collected upon admission and during hospitalization for tuberculosis testing. miR-29a had an overall sensitivity of 82% (95% CI 77, 85%) and an overall specificity of 82% (95% CI 78, 86%) for detecting tuberculosis. DOR was 21 (95% CI 16-28), and the area under the curve was 0.89 (95% CI 0.86, 0.91). miR-29a had slightly different diagnostic efficacy in different specimens. miR-29a showed good performance in both the diagnosis of pulmonary tuberculosis and extrapulmonary tuberculosis. miR-29b and miR-29c also had a good performance in diagnosis of tuberculosis.
CONCLUSION
As can be seen from the diagnostic performance of miR-29, miR-29 can be used as a potential biomarker for the rapid detection of tuberculosis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=461107.
Topics: Humans; MicroRNAs; Biomarkers; Tuberculosis; Sensitivity and Specificity
PubMed: 38807999
DOI: 10.3389/fpubh.2024.1384510 -
PLoS Medicine May 2024India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate...
BACKGROUND
India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India.
METHODS AND FINDINGS
We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population.
CONCLUSIONS
This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade.
Topics: Humans; India; Tuberculosis; Health Services Accessibility; Treatment Outcome; Male
PubMed: 38805509
DOI: 10.1371/journal.pmed.1004409 -
Microorganisms Apr 2024(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT)... (Review)
Review
(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.
PubMed: 38792678
DOI: 10.3390/microorganisms12050847 -
Cancers May 2024We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. (Review)
Review
UNLABELLED
We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients.
METHOD
We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included.
RESULT
The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, low certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01-1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence).
CONCLUSION
We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.
PubMed: 38792012
DOI: 10.3390/cancers16101934