Severe Pneumonia Research Articles

Klebsiella pneumoniae co-infection leads to fatal pneumonia in SARS-CoV-2-infected mice

SARS-CoV-2 patients have been reported to have high rates of secondary Klebsiella pneumoniae infections. K. pneumoniae is a commensal that is typically found in the respiratory and gastrointestinal tracts. However, it can cause severe disease when a person’s immune system is compromised. Despite a high number of K. pneumoniae cases reported in SARS-CoV-2 patients, a co-infection animal model evaluating the pathogenesis is not available. In our cohort of COVID-19-positive human patients, 38% exhibited the presence of K. pneumoniae. Therefore we developed a mouse model to study the disease pathogenesis of SARS-CoV-2 and K. pneumoniae co-infection. BALB/cJ mice were inoculated with mouse-adapted SARS-CoV-2 followed by a challenge with K. pneumoniae. Mice were monitored for body weight change, clinical signs, and survival during infection. The bacterial load, viral titers, immune cell accumulation and phenotype, and histopathology were evaluated in the lungs. The co-infected mice showed severe clinical disease and a higher mortality rate within 48 h of K. pneumoniae administration. The co-infected mice had significantly elevated bacterial load in the lungs, however, viral loads were similar between co-infected and single-infected mice. Histopathology of co-infected mice showed severe bronchointerstitial pneumonia with copious intralesional bacteria. Flow cytometry analysis showed significantly higher numbers of neutrophils and macrophages in the lungs. Collectively, our results demonstrated that co-infection of SARS-CoV-2 with K. pneumoniae causes severe disease with increased mortality in mice.

Predicting Clinical Outcomes in COVID-19 and Pneumonia Patients: A Machine Learning Approach.

In the clinical diagnosis of pneumonia, particularly during the COVID-19 pandemic, individuals who progress to a critical stage requiring mechanical ventilation are classified as mechanically ventilated critically ill patients. Accurately predicting the discharge outcomes for this specific cohort, especially those with COVID-19, is of paramount clinical importance. Missing data, a common issue in medical research, can significantly impact the validity of analyses. In this work, we address this challenge by employing two missing data imputation techniques: multiple imputation and missForest, to enhance data completeness. Additionally, we utilize the smoothly clipped absolute deviation (SCAD) penalized logistic regression method to select significant features. Our real data analysis compares the predictive performances of extreme learning machines, random forests, support vector machines, and XGBoost using 10-fold cross-validation. The results consistently show that XGBoost outperforms the other methods in predicting discharge outcomes, making it a reliable tool for clinical decision-making in the treatment of severe pneumonia, including COVID-19 cases. Within this context, the random forest imputation method generally enhances performance, underscoring its effectiveness in managing missing data compared to multiple imputation.

Fibrotic outcomes from SARS-CoV-2 virus interstitial pneumonia.

Following the onset of the new COVID-19 pandemic, particular attention is paid to the long-term outcomes, especially concerning patients affected by the SARS-CoV-2 virus leading to interstitial pneumonia. The aim of this research is to evaluate the possible evolution over time of interstitial pneumonia into post-inflammatory fibrosing interstitial disease. This research included 42 patients admitted to the COVID ward for SARS-CoV-2 interstitial pneumonia, 10 patients with mild pneumonia and respiratory failure who were treated with O2 only, 32 patients with severe pneumonia in which O2 and non-invasive ventilation were used for respiratory assistance, and 4 patients treated with invasive mechanical ventilation. At 70±30 days, 6, 12, 24, and 36 months after discharge, the cohort of patients carried out the evaluation of inflammation indices, high-resolution computed tomography (CT) chest scans, and functional respiratory tests. The comparative analysis showed that 83.3% of patients had residual parenchymal lung disease at 36-month follow-up, with a significantly higher rate in those with severe pneumonia and more extensive disease on initial CT. Regarding the pulmonary involvement model, patients presented ground-glass opacity or peripheral parenchymal bands, or a combination of them, peri- and intralobular interstitial thickening, which may be representative of fibrotic interstitial lung disease. There is a correlation between the severity of pneumonia, the inflammatory state, the need to increase respiratory support, and the quantity and persistence of CT-related lesions. Reductions in respiratory functions and exercise capacity were observed, the latter more pronounced in patients (24%) who had contracted severe pneumonia and required ventilatory support.Pulmonary outcomes from SARS-CoV-2 respiratory infections show a wide range of radiological findings, from complete recovery to stable outcomes of thickening and distortion of the interstitial architecture. From a functional point of view, there is an impairment of the alveolar-capillary diffusion capacity and, in cases who had contracted severe pneumonia, desaturation and reduced exercise tolerance in 24% of cases at a 36-month follow-up.

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis

BackgroundMacrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children’s health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children.MethodsThis retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student’s t-test, Mann–Whitney U test, and χ2 or Fisher’s exact tests were used for group comparisons.ResultsA total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022).ConclusionDoxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Rapid detection of human adenovirus by multiple cross displacement amplification combined with nanoparticle-based biosensor platform

Human adenoviruses (HAdV), particularly serotypes 3 and 7 (HAdV-3 and HAdV-7), are significant respiratory pathogens that contribute to high morbidity rates and severe pneumonia in infants and children. The lack of distinct clinical presentations and effective treatments highlights the urgent need for rapid and reliable diagnostic methods for HAdV-3 and HAdV-7. This study devises a novel detection assay, termed HAdV-MCDA-LFB, which combines isothermal multiple cross displacement amplification (MCDA) with a nanoparticle-based lateral flow biosensor (LFB). Targeting the conserved hexon gene, HAdV-MCDA-LFB demonstrated high sensitivity, detecting low to 10 fg of hexon-containing plasmid per reaction without cross-reaction under the optimized conditions. Moreover, HAdV-MCDA-LFB exhibited comparable diagnostic accuracy to real-time PCR in clinical sample analysis, indicating its practical applicability. The whole procedure, including rapid template preparation (15 min), MCDA reaction (40 min at 67 °C) and result interpretation (<5 min), can be completed within one hour. Together, this rapid turnaround time, coupled with its simplicity and accuracy, makes HAdV-MCDA-LFB a promising point-of-care diagnostic tool for HAdV-3 and HAdV-7, particularly in resource-limited settings.

Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution

How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9+ macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9+ macrophages contain SARS-CoV-2, recruit and interact with Isg12+Cst7+ neutrophils to clear the viruses. After viral clearance, Slamf9+ macrophages differentiate into Trem2+ and Fbp1+ macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9+ macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.

The effect of corticosteroids in developing active pulmonary tuberculosis among patients with COVID-19.

Corticosteroids can reduce the mortality rate among patients with severe COVID-19 pneumonia. However, opportunistic infections such as Mycobacterium tuberculosis are of concern, especially among those on high doses of corticosteroids. It is unknown whether the risk of developing subsequent TB infection is high or not among COVID-19 patients on high doses of corticosteroids. Hence, this study was conducted to address this gap of knowledge. We conducted a retrospective, cross-sectional study at the King Chulalongkorn Memorial Hospital from October 12, 2022 to June 30, 2023. Two hundred forty-three participants with documented COVID-19 diagnosis on high dose corticosteroids were enrolled into the study. Baseline characteristics and risk factors of developing TB were collected. The prevalence of TB was significantly different among participants with chronic kidney disease (CKD) stages 2-4 and chronic lung diseases. The incidence of TB post 1-year diagnosis of COVID-19 was 4 out of 243 patients (1.6%) or 1,646 cases per 100,000 person-year. The mortality rate among subsequent TB group was significantly much higher than the non-TB group (50% vs 0.4%; p-value = 0.001). COVID-19 participants on high doses of corticosteroids also were co-infected with other infections such as bacteria (37.1%), fungi (5.3%), and Pneumocystis jirovecii (PJP) (1.2%). We found that the incidence of TB in participants with COVID-19 on high doses of corticosteroids was 11 times higher than the general population. Therefore, we recommend screening for latent TB among these patients to prevent/early diagnose TB disease.

Corynebacterium striatum

Abstract Corynebacterium striatum (C. striatum) is a rapidly emerging multidrug-resistant organism commonly found as a skin and respiratory tract commensal. The first case of C. striatum infection was published in 1980 in a patient with chronic lymphocytic leukemia who had a pleuropulmonary infection. The chemotherapeutic agents used in hematologic malignancies completely deplete neutrophils, making them susceptible to various pathogens such as C. striatum, which are rarely pathogenic. The spectrum of presentation due to C. striatum includes severe bloodstream infections, pneumonia, meningitis, and infective endocarditis. Some of the most common risk factors are prolonged neutropenia with various invasive devices and numerous prophylactic antibiotics. This article aims to present three cases of C. striatum infections in immunocompromised patients at H. Lee Moffitt Cancer Centre. In such rare cases, infection prevention and appropriate antibiotic coverage are the key to preventing such infections.

Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection

How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell–T cell immunity hubs, where Ccr7+Ido1+ dendritic cells, Cd160+Cd8+ T cells, and Tnfrsf4+Cd4+ T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9+ macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.

Tissue-Compatible and Lubricated Hydrogel Catheter with Promising Activity Against Polymicrobial Infections for Ventilator-Associated Pneumonia Prevention.

Endotracheal intubation is a vital means of saving critically ill patients. However, the inserted catheter often causes tissue damage and the formation of tenacious biofilms containing drug-resistant bacteria and fungi, leading to severe ventilator-associated pneumonia (VAP). Currently, the resolution of VAP is usually based on antibiotic treatment and lacks targeted prophylaxis. Here, a quaternary phosphonium salts functionalized hydrogel catheter that enhances tissue compatibility yet inhibits complex and tenacious pathogens in the catheter, thus preventing VAP is reported. By copolymerizing the quaternary phosphonium electrolyte and acrylic acid monomers, the hydrogel catheter demonstrates good shape-supporting ability, and its strength and modulus can be adjusted over a wide range to meet the needs of different ages. Moreover, it possesses good tissue compatibility, antifouling properties, stable lubrication capability, and superior hydrophilicity, which may mitigate tissue damage caused by contact. Importantly, the hydrogel catheter demonstrates potent broad-spectrum intrinsic antimicrobial activity, eradicating nearly 99% of multi-drug resistant bacteria and 80% of fungi. To validate its role in preventing VAP, the real VAP pathogenesis process is mimicked, establishing a polymicrobial infections model considering time effects. The results prove that the hydrogel catheter effectively inhibits the invasion of various drug-resistant pathogens and prevents biofilm formation.

The severity assessment and nucleic acid turning-negative-time prediction in COVID-19 patients with COPD using a fused deep learning model

BackgroundPrevious studies have shown that patients with pre-existing chronic obstructive pulmonary diseases (COPD) were more likely to be infected with coronavirus disease (COVID-19) and lead to more severe lung lesions. However, few studies have explored the severity and prognosis of COVID-19 patients with different phenotypes of COPD.PurposeThe aim of this study is to investigate the value of the deep learning and radiomics features for the severity evaluation and the nucleic acid turning-negative time prediction in COVID-19 patients with COPD including two phenotypes of chronic bronchitis predominant patients and emphysema predominant patients.MethodsA total of 281 patients were retrospectively collected from Hohhot First Hospital between October 2022 and January 2023. They were divided to three groups: COVID-19 group of 95 patients, COVID-19 with emphysema group of 94 patients, COVID-19 with chronic bronchitis group of 92 patients. All patients underwent chest computed tomography (CT) scans and recorded clinical data. The U-net model was pretrained to segment the pulmonary involvement area on CT images and the severity of pneumonia were evaluated by the percentage of pulmonary involvement volume to lung volume. The 107 radiomics features were extracted by pyradiomics package. The Spearman method was employed to analyze the correlation of the data and visualize it through a heatmap. Then we establish a deep learning model (model 1) and a fusion model (model 2) combined deep learning with radiomics features to predict nucleic acid turning-negative time.ResultsCOVID-19 patients with emphysema was lowest in the lymphocyte count compared to COVID-19 patients and COVID-19 companied with chronic bronchitis, and they have the most extensive range of pulmonary inflammation. The lymphocyte count was significantly correlated with pulmonary involvement and the time for nucleic acid turning negative (r=-0.145, P < 0.05). Importantly, our results demonstrated that model 2 achieved an accuracy of 80.9% in predicting nucleic acid turning-negative time.ConclusionThe pre-existing emphysema phenotype of COPD severely aggravated the pulmonary involvement of COVID-19 patients. Deep learning and radiomics features may provide more information to accurately predict the nucleic acid turning-negative time, which is expected to play an important role in clinical practice.

Transcriptomic Biomarkers Associated with Microbiological Etiology and Disease Severity in Childhood Pneumonia.

Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches. Using whole blood ribonucleic acid sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed genes that best identified children according to detected microbial pathogens (viral-only vs. bacterial-only and typical vs. atypical bacterial [+/- viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe). Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial (+/- viral co-detections), and 26 (12%) had atypical bacterial (+/- viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (+/- viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including four genes also identified in the viral-only vs. bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and four genes from the typical vs atypical bacterial model (PRSS23, IFI27, OLFM4, and ABO). We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.

Ibrutinib as a Secondary Treatment for Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease: A Case Series of 11 Patients During the COVID-19 Era.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has recently become available for treating chronic graft-versus-host disease (cGVHD). Because the pivotal clinical trials for this approach were conducted before the COVID-19 pandemic, evidence regarding ibrutinib treatment for cGVHD in the COVID-19 era is insufficient. We assessed the safety and efficacy of ibrutinib treatment in a real-world setting by retrospectively analyzing the outcomes of 11 patients with steroid-refractory and steroid-dependent cGVHD who were treated with ibrutinib between November 2021 and April 2024 at our hospital. The best overall response rate was 63.6%, and the steroid dose was successfully reduced in seven of the patients. Ibrutinib improved hemolytic anemia and serositis in some of the patients. The most common adverse events were infections and bleeding. Four of the patients contracted COVID-19 during the study period, of whom one discontinued the treatment because of severe COVID-19 pneumonia. Ibrutinib was effective for treating cGVHD, particularly when B cells were involved in its pathogenesis, and decreased the steroid dose needed for treatment in a real-world setting. Patients should be carefully monitored and treated for adverse events during this treatment, particularly bleeding and any complications associated with COVID-19 infection.

Prognostic value of soluble programmed death-1 and soluble programmed death ligand-1 in severe traumatic brain injury patients

Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission. A total of 20 healthy volunteers and 82 patients were enrolled in this study. The levels of sPD-1 and sPD-L1 were upregulated in patients with severe TBI (P < 0.001). They were significantly increased in the post-TBI severe pneumonia group and among non-survivors (P < 0.001). The area under the curves (AUCs) for sPD-1 and sPD-L1 levels to predict severe pneumonia were 0.714 and 0.696, respectively, and the AUCs to predict mortality were 0.758 and 0.735. The levels of sPD-1 and sPD-L1 are correlated with the GCS scores at admission, APACHE II scores, length of MV, and time elapsed to mortality. The levels of sPD-1 and sPD-L1 emerged as independent predictive factors for severe pneumonia and mortality. This study demonstrates that upregulation of sPD-1 and sPD-L1 in severe TBI patients is significantly associated with severe pneumonia and mortality, suggesting their potential as predictive biomarkers for these outcomes.

Prospective cohort study on the clinical significance of interferon-γ, D-dimer, LDH, and CRP tests in children with severe mycoplasma pneumonia.

Mycoplasma pneumoniae is a significant cause of respiratory infections in children, often leading to severe pneumonia. This study aimed to assess the clinical relevance of interferon-gamma (interferon-γ), D-dimer, lactate dehydrogenase (LDH), and C-reactive protein (CRP) as biomarkers in the severity of mycoplasma pneumonia in pediatric patients. In this prospective study, 203 pediatric patients with mycoplasma pneumonia were classified into mild (123 patients) and severe (80 patients) groups. Biomarkers including interferon-γ, D-dimer, LDH, and CRP were measured and analyzed. Statistical methods employed included Pearson and Spearman correlation analyses, logistic regression, and receiver operating characteristic curve analysis. The severe group exhibited significantly higher median and interquartile ranges for interferon-γ, D-dimer, LDH, and CRP compared to the mild group. Logistic regression identified IL-10, IL-6, interferon-γ, tumor necrosis factor-alpha, D-dimer, and LDH as independent predictors of severity, with the model achieving 92% accuracy. Receiver operating characteristic curve analysis showed optimal diagnostic efficacy for interferon-γ, D-dimer, and LDH, with the best threshold values being 8.11, 0.64, and 379, respectively. A significant positive correlation was observed between IL-6 and LDH, as well as between interferon-γ and D-dimer. This study showed that interferon-γ >8.11, D-dimer >0.64, and LDH >379 have an important role in the assessment of severe mycoplasma pneumonia.

Prognostic Value of Coronary Artery Calcification in Patients with COVID-19 and Interstitial Pneumonia: A Case-Control Study.

Background: Patients suffering from coronavirus disease-19 (COVID-19)-related interstitial pneumonia have variable outcomes, and the risk factors for a more severe course have yet to be comprehensively identified. Cohort studies have suggested that coronary artery calcium (CAC), as estimated at chest computed tomography (CT) scan, correlated with patient outcomes. However, given that the prevalence of CAC is gender- and age-dependent, the influence of baseline confounders cannot be completely excluded. Methods: We designed a retrospective, multicenter case-control study including patients with COVID-19, with severe course cases selected based on death within 30 days or requiring invasive ventilation, whereas controls were age- and sex-matched patients surviving up to 30 days without invasive ventilation. The primary outcome was the analysis of moderate-to-severe CAC prevalence between cases and controls. Results: A total of 65 cases and 130 controls were included in the study. Cases had a significantly higher median pulmonary severity score at chest CT scan compared to controls (10 vs. 8, respectively; p = 0.0001), as well as a higher CAC score (5 vs. 2; p = 0.009). The prevalence of moderate-to-severe CAC in cases was significantly greater (41.5% vs. 23.8%; p = 0.013), a difference mainly driven by a higher prevalence in those who died within 30 days (p = 0.000), rather than those requiring invasive ventilation (p = 0.847). White blood cell count, moderate-to-severe CAC, the need for antibiotic therapy, and severe pneumonia at CT scan were independent primary endpoint predictors. Conclusions: This case-control study demonstrated that the CAC burden was higher in COVID-19 patients who did not survive 30 days or who required mechanical ventilation, and CAC played an independent prognostic role.

Comparison of clinical, laboratory and radiological characteristics between COVID-19 and Chlamydia psittaci pneumonia: a multicenter retrospective study

Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process.

Novel Compound Heterozygous Variants in the FAS Gene Lead to Fetal Onset of Autoimmune Lymphoproliferative Syndrome (ALPS).

FAS gene defects lead to autoimmune lymphoproliferative syndrome (ALPS), which is often inherited in an autosomal dominant and rarely in an autosomal recessive manner. We report a case of a newborn girl with novel compound heterozygous variants in FAS and reveal the underlying mechanism. Whole-exome sequencing (WES) was used to identify pathogenic variants. Multiparametric flow cytometry analysis, phosflow analysis, and FAS-induced apoptosis assays were used to explore the effects of the variants on FAS expression, apoptosis, and immunophenotype. The HEK293T cells were used to assess the impact of the variants on protein expression and FAS-induced apoptosis. The patient was born with hepatosplenomegaly, anemia, and thrombocytopenia. She also experienced COVID-19, rotavirus infection, herpes simplex virus infection, and severe pneumonia. The proportion of double-negative T cells (DNTs) was significantly elevated. Novel FAS compound heterozygous variants c.310T > A (p.C104S) and c.702_704del (p.T235del) were identified. The apoptotic ability of T cells was defective, and FAS expression on the surface of T cells was deficient. The T235del variant decreased FAS expression, and the C104S protein remained in the endoplasmic reticulum (ER) and could not translocate to the cell surface. Both mutations resulted in loss-of-function in terms of FAS-induced apoptosis in HEK293T cells. The DNTs were mainly terminally differentiated T (TEMRA) and CD45RA+HLA-DR+, with high expression of CD85j, PD-1, and CD57. The percentage of Th1, Tfh, and autoreactive B cells were significantly increased in the patient. The abnormal immunophenotyping was partially attenuated by sirolimus treatment. We identified two variants that significantly affect FAS expression or localization, leading to early disease onset of in the fetus. Abnormalities in the mTOR pathway are associated with a favorable response to sirolimus.

Risk factor analysis and prediction model construction for severe adenovirus pneumonia in children

BackgroundSevere adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease.MethodsA retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children’s Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated.Results699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963–0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power.ConclusionIn this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value.

Combined local flap placement and negative-pressure wound therapy for the management of critical peritracheostomal pharyngocutaneous fistula

ObjectivePeritracheostomal pharyngocutaneous fistula (PCF), a direct connection between the PCF and tracheal stoma due to a skin defect, is among the most problematic complications after total laryngectomy or pharyngolaryngectomy. Peritracheostomal PCFs can cause lethal complications, including severe pneumonia or carotid blowout, secondary to salivary leakage directly into the tracheal stoma, and their management is challenging without early invasive surgical closure. We aimed to evaluate the utility of our novel and minimally invasive combined local skin flap placement and negative-pressure wound therapy (NPWT) method for the management and conservative closure of peritracheostomal PCFs. MethodsWe retrospectively enrolled patients who developed a peritracheostomal PCF from July 2015 to September 2021 at our institution and affiliated hospitals. Postoperative PCFs were all initially managed with appropriate wound bed preparation. Subsequently, a small local flap of healthy, lower neck skin was elevated and transferred anterior to the PCF to replace the peritracheostomal skin defect. The flap served to provide a sufficient surface for film dressing attachment and facilitated airtight sealing during NPWT. We initiated NPWT after confirming the local skin flap was firmly sutured to the tracheal mucosa. A flexible hydrocolloid dressing was applied to the peritracheostomal skin flap, and a film dressing was placed on the flexible hydrocolloid dressing and surrounding cervical skin. We inserted the NPWT foam shallowly into the fistula tract and applied negative pressure (73.5–125 mmHg). NPWT was continued until the PCF was closed or became so small that salivary leakage was minimal and could be managed by conventional compression dressings. ResultsWe enrolled six patients [male, n = 6; mean age, 66.5 years (range, 57–80 years)]. NPWT was applied for an average of 18.2 days (range, 2–28 days). During NPWT, air leakage occurred once (2 cases), only a few times (2 cases), or not at all (2 cases). In all patients, complete fistula closure was achieved in an average of 28.2 days (range, 15–55 days) after the start of NPWT, and no patient required further surgical intervention. There were no lethal complications (e.g., severe pneumonia) during treatment. ConclusionOur method of combined local flap placement and NPWT enabled effective management of salivary aspiration and accelerated wound healing, which allowed conservative fistula closure in all patients. We believe combined local flap placement and NPWT should be considered a first-line treatment for intractable peritracheostomal PCF.