Significance of the Modified NUTRIC Score for Predicting Clinical Outcomes in Patients with Severe Community-Acquired Pneumonia

Nutritional status could affect clinical outcomes in critical patients. We aimed to determine the prognostic accuracy of the modified Nutrition Risk in Critically Ill (mNUTRIC) score for hospital mortality and treatment outcomes in patients with severe community-acquired pneumonia (SCAP) compared to other clinical prediction rules. We enrolled SCAP patients in a multi-center setting retrospectively. The mNUTRIC score and clinical prediction rules for pneumonia, as well as clinical factors, were calculated and recorded. Clinical outcomes, including mortality status and treatment outcome, were assessed after the patient was discharged. We used the receiver operating characteristic (ROC) curve method and multivariate logistic regression analysis to determine the prognostic accuracy of the mNUTRIC score for predicting clinical outcomes compared to clinical prediction rules, while 815 SCAP patients were enrolled. ROC curve analysis showed that the mNUTRIC score was the most effective at predicting each clinical outcome and had the highest area under the ROC curve value. The cut-off value for predicting clinical outcomes was 5.5. By multivariate logistic regression analysis, the mNUTRIC score was also an independent predictor of both clinical outcomes in SCAP patients. We concluded that the mNUTRIC score is a better prognostic factor for predicting clinical outcomes in SCAP patients compared to other clinical prediction rules.

Ampicillin & Gentamicin V/S 3rd Generation Cephalosporin for the Management of Community-Acquired Pneumonia in Children; A Comparative Analysis

Background: Community acquired pneumonia (CAP) is a common cause of childhood morbidity, attributed to every 1 in 500 hospitalization of children under the age of 5 years. While science made therapeutic advancements to battle CAP, the pathogens too have acquired resistance to many drugs. In this fight for dominance, Ampicillin plus Gentamicin and 3rd Gen Cephalosporins are nowadays the cornerstone of treatment. However, their efficacy varies in different parts of the world owing to differing levels of drug resistance. Objective: To compare the effect of Ampicillin and Gentamicin vs. third generation cephalosporin in treatment of severe community acquired pneumonia. Methodology: This Randomized Controlled Trial was conducted at the Dept. of Pediatrics (Ziauddin University Hospital) upon a sample of 74 patients (in two equal groups) of either gender, aged 2 months to 5 years, presenting with CAP. After taking written informed consent, data was recorded onto a pre-structured questionnaire containing inquiries pertaining to basic biodata, sociodemographic details, presenting complaints, immunization status of the pneumococcal and HIB vaccine, laboratory values, and treatment outcome. Results: The mean age of the sample stood at 15 months (SD ± 3) with a majority of the sample comprising of male children (52.7%). The mean weight stood at 8.7 kg (SD ± 0.9) and the mean height was recorded to be 74.2 cm (SD ± 11). The commonest symptoms included fever, fast breathing, chest in-drawing and added sounds. It was revealed that both treatments achieved successful treatment outcomes in all patients with no mortality. The resolution of symptoms however varied with faster resolution observed in the Cephalosporin group. Conclusion: After careful consideration, it can be concluded that 3rd generation cephalosporins is more efficacious at treatment of CAP with significantly faster resolution of disease symptoms.

Impairment of Neutrophil Functions and Homeostasis in COVID-19 Patients: Association With Disease Severity

Background Emerging data based on analyses of peripheral and pulmonary immune responses to SARS-CoV-2 increasingly suggest that a dysregulated immune response underpins the development of severe disease in COVID-19 patients. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. Methods This longitudinal study compares study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2 – patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. Results At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets — both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide, an abnormality that was greater in superinfected than non-superinfected COVID-19 patients. Moreover, patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. Conclusions These data suggest that neutrophil exhaustion may play a central role in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.

Efficacy of azoximer bromide in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia

Introduction. The high incidence of community-acquired pneumonia and the high complication rates in the cases of severe pneumonia actualize the search for new pharmacotherapy tools to improve the effectiveness of standard patient management regimens. A high level of severe inflammatory response underlies the high risk for developing septic complications of pneumonia, along with impaired immune responses.The aim is to evaluate the efficacy of azoximer bromide introduction in the combination therapy regimen for hospitalized patients with moderate to severe community-acquired pneumonia.Materials and methods. A prospective, open label, parallel group, randomized study comparing the efficacy of azoximer bromide introduction in the combination therapy of hospitalized patients with moderate to severe community-acquired pneumonia was conducted at the premises of Federal Scientific and Clinical Center for Reanimatology and Rehabilitation. 30 patients were included in the study group and 37 patients in the comparator group. The baseline characteristics were comparable in both groups. Results. The azoximer bromide introduction in the combination therapy of patients with community-acquired pneumonia led to a statistically significant reduction in the duration of hospital stay (Me (LQ; HQ): 9 (8; 10) days for the study group and 13 (10; 14) days for the comparator group, (p = 0.000078), duration of ICU stay (Me (LQ; HQ) 2 days (1.5; 2.5) and 5 days (5.0; 6.0), respectively, (p = 0.00001), the duration of febrile fever 5 (± 0.6) days versus 10 (± 1.2) days (p = 0.0000), the incidence of acute respiratory failure (13.33% in group 1 versus 37.84% in group 2, p = 0.024) and septic shock (10% in group 1 versus 32.43% in group 2, p = 0.0285).Conclusions. The azoximer bromide introduction in the standard therapy regimen for patients with community-acquired pneumonia allowed to reduce the duration of hospital stay, the duration of ICU stay, the length of febrile fever, the incidence of septic shock and respiratory failure. The possible mechanisms of action may include a reduction of the severe inflammatory reactions and an optimization of the patient's immune response to the infectious process.

Clinical characteristics and risk factors associated with mortality in patients with severe community-acquired pneumonia and type 2 diabetes mellitus

Background The present study was performed to investigate the impacts of type 2 diabetes mellitus (T2DM) on severe community-acquired pneumonia (SCAP) and to develop a novel prediction model for mortality in SCAP patients with T2DM. Methods This was a retrospective observational study conducted in consecutive adult patients with SCAP admitted to the intensive care unit (ICU) of West China Hospital, Sichuan University, China, between September 2011 and September 2019. The primary outcome was hospital mortality. A propensity score matching (PSM) analysis model with a 1:2 ratio was used for the comparisons of clinical characteristics and outcomes between T2DM and nondiabetic patients. The independent risk factors were identified via univariate and then multivariable logistic regression analysis and were then used to establish a nomogram. Results In total, 1262 SCAP patients with T2DM and 2524 matched patients without T2DM were included after PSM. Patients with T2DM had longer ICU length of stay (LOS) (13 vs. 12 days, P = 0.016) and higher 14-day mortality (15% vs. 10.8%, P < 0.001), 30-day mortality (25.7% vs. 22.7%, P = 0.046), ICU mortality (30.8% vs. 26.5%, P = 0.005), and hospital mortality (35.2% vs. 31.0%, P = 0.009) than those without T2DM. In SCAP patients with T2DM, the independent risk factors for hospital mortality were increased numbers of comorbidities and diabetes-related complications; elevated C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), brain natriuretic peptide (BNP) and blood lactate; as well as decreased blood pressure on admission. The nomogram had a C index of 0.907 (95% CI: 0.888, 0.927) in the training set and 0.873 (95% CI: 0.836, 0.911) in the testing set, which was superior to the pneumonia severity index (PSI, AUC: 0.809, 95% CI: 0.785, 0.833). The calibration curve and decision curve analysis (DCA) also demonstrated its accuracy and applicability. Conclusions SCAP patients with T2DM had worse clinical outcomes than nondiabetic patients. The nomogram has good predictive performance for hospital mortality and might be generally applied after more external validations.

Serum Vitamin D Level and Risk of Community-Acquired Pneumonia: A Case-Control Study

Introduction. Recent research has shown conflicting evidence on the connection between vitamin D deficiency and community-acquired pneumonia (CAP) in children. Thus, we hypothesized that vitamin D deficiency could be a risk factor for CAP. Methods. Hospitalized children between 2 and 60 months with physician-diagnosed, radiologically confirmed severe community-acquired pneumonia (CAP) were enrolled as cases. Age-matched controls were enrolled from immunization and weighing clinics. A blood sample was collected to assess serum 25-(OH)D concentration. Unconditional logistic regression was done to examine the independent association of vitamin D level with community-acquired pneumonia. Results. Seventy-four children (females: 68%) were included. Overall, 27% had vitamin D deficiency (<20 ng/mL) and 37.8% had insufficiency (20–29 ng/mL). The vitamin D level ranged from 8.67 to 46.2 ng/mL. There was no statistically significant difference in 25(OH)D levels in controls and cases ( p = 0.694 ). In unconditional logistic regression, 25(OH)D concentration was not a determinant of CAP (OR: 0.99, CI: 0.937–1.044, p = 0.689 ). This lack of association remained after adjustment for age, gender, income, crowding, and exposure to passive smoke (OR: 0.99, CI: 0.937–1.065, p = 0.973 ). Household income was significantly associated with CAP (OR: 0.11, 95% CI: 0.021–0.567, p = 0.008 ). Conclusion. Two-thirds of the children with CAP had vitamin D deficiency/insufficiency. In comparison with healthy controls, vitamin D level was not a significant determinant of community-acquired pneumonia. It informs that further multisite research is required using more rigorous scientific methods for conclusive evidence on the relationship between vitamin D and CAP.

Cytokine concentrations in bronchoalveolar lavage fluid (BALF) from children with severe community-acquired pneumonia (SCAP) from Shanghai

Background: It has been well known that overreaction of host immune systems plays a critical role in severe community-acquired pneumonia (SCAP). However, few of previous studies focused on the association between cytokine concentrations in bronchoalveolar lavage fluid (BALF) and SCAP. Object: We examined cytokine concentrations in BALF from children with SCAP and explored predictive value of cytokine concentrations for SCAP. Method: It was a retrospective study. A total of 100 children with SCAP who underwent parallel bronchoalveolar lavage between July 2017 and June 2019 were enrolled. 100 patients with mild community-acquired pneumonia (MCAP) who were admitted to the hospital were matched based on age and sex during the same time period . Basic clinical information were collected. Flow cytometry was used to determine the cytokine concentrations in BALF. Receiver operating characteristic curve was used to analyze their predictive value for SCAP. Result: A total of 106 males and 94 females were included in this study. The results showed that the CRP, PCT, ESR, LDH, and D-dimer were significantly increased in the SCAP group. The SCAP patients also had longer fever duration, hospitalization stays, and higher hospitalization costs. The IL-5，IL-17A，IL-18，and TnF-α in BALF of SCAP group were significantly higher than those in MCAP group. ROC curve analysis demonstrated AUC of those cytokines were all among 0.5~0.7. Conclusion: The IL-5，IL-17A，IL-18，and TnF-α in BALF of children with SCAP group were highe. However, the efficacy of those cytokines in the clinical diagnosis of SCAP is not excellent to be used as a predictor.

Microbiota of the lower respiratory tract in community-acquired pneumonia, including cases associated with SARS-CoV-2

Introduction. Many aspects of the pathogenesis and pathomorphology of pneumonia associated with novel coronavirus require a comprehensive study using modern diagnostic methods.The aim of the study was to study the microbiota of the lower respiratory tract in community-acquired pneumonia associated with SARS-CoV-2, to assess the antibiotic and phage resistance of circulating strains of microorganisms.Materials and methods. The analysis of biosamples from 486 patients undergoing inpatient treatment in five mono-hospitals in Tyumen and Tyumen region with a diagnosis of moderate and severe community-acquired pneumonia was carried out. In almost 90% of cases patients received oxygen therapy, about 8% of patients were connected to ventilators. The inoculation of the cultures with clinical samples was carried out for six months (from April to October 2020). The isolated bacterial strains were identified by mass spectrometry. The resistance to antimicrobial drugs and bacteriophages was assessed for identified isolated.Results. Gram-positive cocci, mainly opportunistic microorganisms of the genus Streptococcus and Candida fungi predominated in the microbiota of the lower respiratory tract of patients diagnosed with community-acquired pneumonia associated with SARS-CoV-2. At the same time, bacteria of the Enterobacteriaceae family and nonfermenting gram-negative bacteria were less common compared to patients without coronavirus infection. In the structure of pathogens, the leading position was occupied by the bacteria K. pneumoniae and Acinetobacter spp. The analysis of the sensitivity of microorganisms to antimicrobial drugs showed the highest resistance rates in strains of Acinetobacter spp., Enterococcus spp., Coagulase-negative Staphylococcus. It has been established that in the group of patients with community-acquired pneumonia associated with SARS-CoV-2, the risk of infection with Streptococcus spp. with high level of antibiotic resistance was 1.5 times higher, and taking into account the 95% confidence interval, the value of this indicator ranged from 1.1 to 2.1 times.Conclusion. The data obtained indicate that the microbiota of the lower respiratory tract in community-acquired pneumonia associated with SARS-CoV-2 is represented mainly by bacteria of the genus Streptococcus, which have a high level of resistance to antimicrobial drugs.

Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia

Objective: The aim of this study was to investigate possible associations between Heparin-binding protein (HBP) and the development of respiratory failure (RF) and sepsis in critically ill children with severe community-acquired pneumonia (CAP).Methods: This study enrolled 157 children with severe CAP admitted to Intensive Care Unit (ICU). At ICU admission, the levels of HBP and other biomarkers, including C-reactive protein, interleukin-6 (IL-6), procalcitonin, white blood cells, neutrophil percentage, and D-dimer, were determined.Results: Of the enrolled patients, 106 developed RF (35 with RF at enrollment and 71 with RF after enrollment), while 51 did not developed RF. The number of patients progressing to sepsis in those with or without RF were 34 (21 with severe sepsis) and 14, respectively. The plasma level of HBP at admission was more than eightfold higher than the upper normal value. HBP, IL-6, and D-dimer could significantly predict the development of RF, and a high level of HBP (odds ratio = 1.008, 95% confidence interval: 1.003–1.013) was independently associated with the development of RF in this population. Compared with other biomarkers, HBP was the best indicator of progression to severe sepsis, with an area under the receiver operating characteristic curve of 0.85, the best specificity at 96.30%, and a positive predictive value of 92.86% at the optimal cut-off value of 340.29 ng/mL. The HBP level was also positively correlated with other conventional biomarkers.Conclusion: HBP might represent a better predictor of disease progression in children with severe CAP than currently used biomarkers.