BACKGROUND

Differentiating bacterial from aseptic meningitis in children is critical for optimal treatment. While symptoms overlap, bacterial meningitis demands immediate antibiotics. Traditionally, CSF culture has been the gold standard for diagnosis, but its yield has declined with widespread vaccination. Consequently, some children with negative cultures may still have bacterial meningitis. The Bacterial Meningitis Score (BMS), a validated clinical prediction rule, offers a valuable tool, particularly in resource-limited settings, to better identify high-risk children and guide more effective treatment strategies.

To evaluate the clinical utility and diagnostic accuracy of the BMS in identifying pediatric patients at high risk for bacterial meningitis.

This retrospective cross-sectional study included 75 pediatric patients (aged 29 days to 18 years) with suspected meningitis seen at the Emergency Room of the Pediatrics Department in Mariano Marcos Memorial Hospital and Medical Center from March to November 2023. Eligible patients underwent lumbar puncture for CSF analysis. The BMS, a five-variable clinical tool including CSF Gram stain, CSF absolute neutrophil count, CSF protein, peripheral absolute neutrophil count, and seizure, were used to classify patients as very low risk (BMS=0) or not very low risk (BMS ≥1).

The diagnostic performance of the Bacterial Meningitis Score (BMS) across different cut-off thresholds is as follows: At a cutoff of ≥1, sensitivity is 100%, specificity is 36.80%, positive predictive value (PPV) is 33.3% (95% CI: 22% – 46%), negative predictive value (NPV) is 100% (95% CI: 84.5% – 100%), positive likelihood ratio (LR+) is 1.58 (95% CI: 1.29 – 1.93), negative likelihood ratio (LR–) is 0 (95% CI: 0 – NaN), and Youden’s index is 0.36. For a cut-off of ≥2, sensitivity is 88.90%, specificity is 78.90%, PPV is 57% (95% CI: 39% – 73%), NPV is 95% (95% CI: 85% – 98%), LR+ is 4.21 (95% CI: 2.48 – 7.16), LR– is 0.14 (95% CI: 0.03 – 0.52), and Youden’s index is 0.67. At a cut-off of ≥3, sensitivity drops to 61.10%, specificity increases to 98.20%, PPV rises to 91% (95% CI: 64% – 98%), NPV is 88%(95% CI: 78% – 94%), LR+ is 33.94 (95% CI: 4.82 – 251.61), LR– is 0.39 (95% CI: 0.22 – 0.70), and Youden’s index is 0.59. Finally, at a cut-off of ≥4, sensitivity is markedly low at 5.56%, specificity is perfect at 100%, PPV is 100% (95% CI: 20% – 100%), NPV is 77% (95% CI: 66% – 85%), LR+ is not applicable, LR– is 0.94 (95% CI: 0.84 – 1.05), and Youden’s index is 0.056. The optimal cutoff based on Youden’s index (0.67) was BMS ≥2, providing a more balanced trade-off between sensitivity (88.90%) and specificity (78.90%).

The BMS is a highly sensitive initial screen for bacterial meningitis in children, but its low specificity at the ≥1 cutoff necessitates a more judicious approach. Employing a ≥2 cutoff (Youden index 0.67) significantly improves diagnostic accuracy, optimizing resource utilization and enabling targeted interventions. While definitive diagnosis requires confirmatory testing, the BMS strategically guides initial triage, particularly crucial in resource-constrained environments.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic pulmonary infection that commonly occurs in immunocompromised children. We report a case of infantile leukemia complicated by PJP and review the relevant literature. A summary and analysis of 10 infantile leukemia patients with PJP infection (9 cases reported in the literature and 1 case from our center) showed that PJP mostly occurred in the early stages of chemotherapy (80%, 8/10). The main clinical manifestations were dyspnea (100%, 10/10) and hypoxemia (50%, 5/10), while pulmonary imaging findings lacked specificity. In most cases (50%, 5/10), diagnosis was established by identifying pathogens in bronchoalveolar lavage fluid under microscopy. In our case, diagnosis was confirmed using targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid. Treatment with intravenous sulfamethoxazole complex was administered in 8 patients, all of whom eventually recovered. PJP may occur in the early stages of chemotherapy for infantile leukemia, thus early prevention is necessary. tNGS facilitates early diagnosis of PJP, and sulfamethoxazole complex remains an effective therapeutic option.
Humans ; Infant ; Bronchoalveolar Lavage Fluid/microbiology* ; Immunocompromised Host ; Leukemia/complications* ; Pneumocystis carinii/isolation & purification* ; Pneumonia, Pneumocystis/diagnosis* ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use*

BACKGROUND: There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA). METHODS: This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods. RESULTS: The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment. CONCLUSIONS A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans ; Tomography, X-Ray Computed/methods* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Artificial Intelligence ; Aged ; Pneumonia/diagnosis* ; Latent Class Analysis ; Adult

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking

BACKGROUND AND OBJECTIVE

COVID-19 contributes significantly to global morbidity and mortality. Age-related comorbidities elevate the risk of severe cases. Studies have recently demonstrated that widely available medications, including tocilizumab (TCZ), can manage severe symptoms. However, its effectiveness is unclear, particularly among the older population. Therefore, this review aimed to evaluate TCZ’s efficacy in managing severe pneumonia in individuals aged 50 and older.

We systematically search several databases and gray literature including Web of Science, CINAHL, Academic Search Complete, PsycINFO, PsycArticles, SocINDEX, CENTRAL/Cochrane Library, PubMed/MEDLINE for original research articles in English across several study designs published in the year 2020-2022. A narrative synthesis was conducted to summarize the evidence. We employed the NIH quality assessment tool for observational cohort studies to evaluate risk of bias. Additionally, we utilized GRADE to appraise the certainty of evidence.

Among 539 screened articles, only five studies met the selection criteria. Tocilizumab's impact on severe COVID-19 pneumonia revealed a diverse effect on mortality rate, with 29% in the TCZ group, and 40% in the controls died within 30 days of intubation (OR 0.61; 95% CI, 0.27-1.36). It is also reported that TCZ was not associated with mortality, despite faster decline in pulmonary function and prolonged fever. Hospital mortality in the TCZ group was significantly lower than in the controls, and age over 60 was the only significant risk factor. Moreover, administering TCZ reduced mechanical ventilation needs, with 82% extubated compared to 53% in controls. However, 45% in TCZ group was associated with a higher ventilator-associated pneumonia rate than in the untreated group which was 20% (P CONCLUSIONS

The effects of tocilizumab on reducing mortality risk and improving the survival rate of COVID-19 patients with pneumonia remained inconclusive. Yet, the majority of results suggested that giving tocilizumab leads to shorter hospital stays, lowers the requirement for mechanical ventilation, and decreases the likelihood of ICU transfer. Tocilizumab is linked to the incidence of secondary infections; hence, this medication should be closely monitored for side effects.

BACKGROUND AND OBJECTIVES

The etiology of pneumonia in the pediatric population varies by age group. Among patients one month to 59 months old, viral pathogens are the most common cause of lower respiratory infections. The study aims to determine the frequency distribution of antibiotic prescription among patients one month to 59 months old and to determine the adherence of primary care facilities to local guidelines with recommended antibiotics.

A descriptive retrospective study using electronic medical records was conducted at two primary care sites. Patients aged 1 month to 59 months old seeking consult via telemedicine or face-to-face diagnosed with community acquired pneumonia from April 2019-March 2020 in the rural facility and May 2019-April 2020 in the remote facility were included in the study. The primary outcome was to determine the patterns of antibiotic use in pneumonia in remote and rural areas and adherence to the recommended antibiotics by the 2016 Philippine Academy of Pediatric Pulmonologists pediatric community-acquired pneumonia clinical practice guidelines (CPG).

There were 30 pediatric patients diagnosed with pneumonia in the rural facility and 213 in the remote facility. Of these patients with pneumonia, 96.7% and 94.8% were prescribed antibiotics in the rural and remote sites, respectively. The most commonly prescribed antibiotic in the rural facility was co-amoxiclav (26.7%), while amoxicillin (51.6%) was the most common in the remote facility. Adherence to the CPG in the rural site was lower at 23.3% (n=8/30) compared to the remote site which was 55.9% (n=119/213).

Primary care physicians prescribed antibiotics in over 90% of the time upon the diagnosis of pneumonia in children aged one month to 59 months old, despite viral pneumonia being the more common in primary care setting. Adherence to recommended antibiotics was higher in the remote setting than in the rural setting. Use of EMR to monitor quality of care can improve patient outcomes and safety, pointing out the importance of improving the quality of documentation in the study sites.

Humans ; Bronchiolitis Obliterans/etiology* ; Early Diagnosis ; Pneumonia, Mycoplasma/complications* ; Consensus ; Child ; Mycoplasma pneumoniae ; China/epidemiology* ; Mass Screening ; Adenoviridae Infections/complications*

Aromatic traditional Chinese medicine(TCM) has played an important role against epidemics and viruses, and volatile components are the main components that exert the pharmacological effects of aromatic TCM. By screening the related monomer components in aromatic TCM against epidemic and viruses and analyzing and endowing TCM with medicinal properties based on its clinical application and pharmacological research according to the theoretical thinking of TCM, the key technical issues of compatibility of TCM monomer components were solved from a theoretical perspective, providing new ideas and methods for screening raw materials and formulas for the development of new TCM drugs. Based on the conditions of antiviral activity, clinical application foundation, definite therapeutic effect, and high safety, a gradient screening of aromatic TCM was carried out. Firstly, 30 aromatic TCM were screened from anti-epidemic literature and clinical trial formulas, and seven volatile monomers were further screened from them. Then, four monomer components with significant effects, namely patchouli alcohol, carvacrol, p-cymene, and eucalyptol were screened. By adopting the "four-step method for a systematic study of TCM properties", the four monomer components were endowed with medicinal properties, and compatibility and combination studies were conducted to explore the theoretical basis of monomer formulas and form monomer formulas guided by TCM theory. The screening results of volatile monomers in aromatic TCM against viral pneumonia included patchouli alcohol, carvacrol, p-cymene, and eucalyptol. The medicinal properties and compatibility theory of volatile monomer components in TCM were explored. Patchouli alcohol was the main herb, with a cool and pungent nature. It entered the lung meridian to dispel evil Qi and has the effects of aromatization, detoxification, and epidemic prevention. Carvacrol was a minister drug with a cool and pungent taste. It had the effects of aromatizing, moistening, and dissolving the exterior, as well as strengthening the spleen and stomach. p-Cymene was an adjunctive medicine with a mild and pungent nature. It entered the lungs and kidneys and had the effects of aromatic purification, cough relief, and asthma relief. Eucalyptol was also an adjunctive medicine with a pungent and warm taste. It had the functions of aromatic purification, cough relief, phlegm reduction, and pain relief. The combination of the four medicines had the effects of aromatizing, moistening, detoxifying, and epidemic prevention, as well as relieving cough and asthma and strengthening the spleen and stomach. They were used to treat viral pneumonia caused by upper respiratory tract viral infections, with symptoms such as chest tightness, cough, wheezing, fatigue, nasal congestion, runny nose, nausea, and vomiting. This study has laid a literature and theoretical foundation for further drug efficacy verification experiments, compatibility efficacy experiments, and subsequent product development and clinical applications, and it serves as an innovative practice that combines literature research, theoretical research, experimental research, and clinical practice to develop new products.
Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/pharmacology* ; Humans ; Pneumonia, Viral/virology* ; Medicine, Chinese Traditional ; Volatile Organic Compounds/pharmacology* ; Animals

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Objectives To investigate interleukin 36γ (IL-36γ) expression, and analyze the influence of IL-36γ to CD8⁺ T cell activity in chronic obstructive pulmonary diseases (COPD) patients with secondary fungal pneumonia. Methods Peripheral blood was collected from 47 COPD patients, 39 COPD patients with secondary fungal pneumonia, and 20 controls. Bronchial alveolar lavage fluid (BALF) was isolated from 27 COPD patients with secondary fungal pneumonia. CD8⁺ T cells were purified. The levels of four IL-36 isoforms in plasma and BALF were measured by enzyme linked immunosorbent assay (ELISA). CD8⁺ T cells were stimulated with recombinant human IL-36γ. The levels of interferon γ(IFN-γ), tumor necrosis factor α(TNF-α), perforin and granzyme B in the cultured supernatants were measured by ELISA. Recombinant human IL-36γ-stimulated CD8⁺ T cells were co-cultured with NCI-H1882 cells in either direct cell-to-cell contact or Transwell^TM manner. The levels of IFN-γ, TNF-α, and lactate dehydrogenase in the cultured supernatants were assessed. The percentage of target cell death was calculated. Results Plasma IL-36α, IL-36β, and IL-36γ levels were significantly elevated in both COPD group and COPD with secondary fungal pneumonia group compared with those in control group. However, only plasma IL-36γ level was higher in COPD with secondary fungal pneumonia group than that in COPD group [(200.11±99.95)pg/mL vs (53.03±87.18)pg/mL, P=0.023]. There was no remarkable difference in plasma IL-36 receptor antagonist level among three groups. IL-36γ level in BALF from infectious site was higher than that from non-infectious site in COPD with secondary fungal pneumonia group [(305.82±59.60)pg/mL vs (251.93±76.01)pg/mL, P=0.011]. IL-36γ stimulation enhanced IFN-γ, TNF-α, perforin and granzyme B secreted by CD8⁺ T cells. When IL-36γ-stimulated CD8⁺ T cells were directly mixed with NCI-H1882 cells for co-culture, the percentage of cell death was increased [(16.06±3.67)% vs (11.47±2.36)%, P=0.002]. When using Transwell^TM plate for non-contact co-culture, IL-36γ-stimulated CD8⁺ T cell-mediated death of NCI-H1882 cells showed no significant difference compared to that without stimulation [(4.77±0.78)% vs (4.99±0.92)%, P=0.554]. Conclusion IL-36γ level in plasma and infectious site is elevated in COPD patients with secondary fungal pneumonia, which enhances the cytotoxicity of CD8⁺ T cells in peripheral blood and infectious microenviroment.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Aged ; Middle Aged ; Interferon-gamma/metabolism* ; Interleukin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Lung Diseases, Fungal/complications* ; Bronchoalveolar Lavage Fluid/chemistry* ; Perforin/metabolism* ; Pneumonia/immunology* ; Granzymes/metabolism*