Risk Of Bacterial Pneumonia Research Articles

Genetically defined causal effects of natural killer cells related traits in risk of infection: a Mendelian randomization study

BackgroundThe intricate interplay between genetics and immunology often dictates the host’s susceptibility to various diseases. This study explored the genetic causal relationship between natural killer (NK) cell-related traits and the risk of infection.MethodsSingle-nucleotide polymorphisms (SNPs) significantly associated with NK cell-related traits were selected as instrumental variables to estimate their genetic causal effects on infection. SNPs from a genome-wide association study (GWAS) on NK cell-related traits, including absolute cell counts, median fluorescence intensities reflecting surface antigen levels, and relative cell counts, were used as exposure instruments. Summary-level GWAS statistics of four phenotypes of infection were used as the outcome data. The exposure and outcome data were analyzed via the two-sample Mendelian randomization method.ResultsEach one standard deviation increase in the expression level of human leukocyte antigen (HLA)-DR on HLA-DR+ NK cells was associated with a lower risk of pneumonia (P < 0.05). An increased HLA-DR+ NK/CD3− lymphocyte ratio was related to a lower of risk of pneumonia (P < 0.05). Each one standard deviation increase in the absolute count of HLA-DR+ NK cells was associated with a lower risk of both bacterial pneumonia and pneumonia (P < 0.05). An increased HLA-DR+ NK/NK ratio was associated with a decreased risk of both pneumonia and bacterial pneumonia (P < 0.05). The results were robust under all sensitivity analyses. No evidence for heterogeneity, pleiotropy, or potential reverse causality was detected. Notably, our analysis did not reveal any significant associations between NK cell-related traits and other phenotypes of infection, including cellulitis, cystitis, and intestinal infection.ConclusionsHLA-DR+ NK cells could be a novel immune cell trait associated with a lower risk of bacterial pneumonia or pneumonia.

Increased risk of bacterial pneumonia before and after respiratory syncytial virus infection in young children.

The burden of respiratory disease is great among children. This study aimed to examine the temporal relationship between hospitalisation for respiratory syncytial virus (RSV) and bacterial pneumonia. A Swedish population-based cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Children born between 1998 and 2015 were included and followed for 2 years. We examined the temporal relationship between RSV hospitalisation and bacterial pneumonia using piecewise exponential models. The final cohort comprised 1 641 747 children, 48.5% were females. There were 23 632 RSV and 4722 bacterial pneumonia hospitalisations, with mean age of 137.8 and 424.2 days, respectively. RSV hospitalisation was associated with bacterial pneumonia with an adjusted incidence rate ratio (aIRR) of 3.18. The risk was highest in the first month after RSV hospitalisation, aIRR 11.19. The risk of bacterial pneumonia was elevated for 4 months after RSV hospitalisation and before RSV hospitalisation. We found an increased risk for bacterial pneumonia hospitalisation in children hospitalised for RSV both before and after RSV hospitalisation, indicating a bidirectional relationship.

CHIPing away at immunity: the role of clonal hematopoiesis of indeterminate potential in bacterial pneumonia.

The occurrence of clonal hematopoiesis of indeterminate potential (CHIP), in which advantageous somatic mutations result in the clonal expansion of blood cells, increases with age, as do an increased risk of mortality and detrimental outcomes associated with CHIP. However, the role of CHIP in susceptibility to pulmonary infections, which also increase with age, is unclear. In this issue of the JCI, Quin and colleagues explored the role of CHIP in bacterial pneumonia. Using characterization of immune cells from human donors and mice lacking tet methylcytosine dioxygenase 2 (Tet2), the authors mechanistically link myeloid immune cell dysfunction to CHIP-mediated risk of bacterial pneumonia. The findings suggest that CHIP drives inflammaging and immune senescence, and provide Tet2 status in older adults as a potential prognostic tool for informing treatment options related to immune modulation.

A randomized control trial investigating the effectiveness of a commercial pneumonia vaccine (part I): Pre-weaned lambs

The objective of this controlled vaccine field trial was to determine the effectiveness of a commercial bacterin in increasing colostral immunity to reduce the risk of bacterial pneumonia in pre-weaned lambs in a commercial sheep operation. Pregnant ewes were randomly allocated to vaccination group (Ovipast™ Plus bacterin, n = 1807; unvaccinated, n = 1812). Ewe vaccination did not significantly (P > 0.05) improve lamb pneumonia treatment rates, crude or pneumonia specific mortality rates, or body weight gain. Interestingly, as birth weight increased in lambs from vaccinated ewes, they gained significantly more than lambs from unvaccinated ewes (P = 0.01). There was no difference in culture results from pneumonic lung samples for either Mannheimia haemolytica (P = 0.89) or Bibersteinia trehalosi (P = 1.00) between lambs from vaccinated and unvaccinated ewes. The results of this study suggest that there was no animal health and welfare benefit from vaccinating ewes with the Ovipast™ Plus bacterin prior to parturition to boost colostral immunity and improve health and growth in their lambs.

Associations between ticagrelor use and the risk of infections: A Mendelian randomization study.

We conducted a Mendelian randomization (MR) study to elucidate the anti-infective effects of ticagrelor. Single-nucleotide polymorphisms (SNPs) associated with serum levels of ticagrelor or its major metabolite AR-C124910XX (ARC) in the PLATelet inhibition and patient Outcomes trial were selected as genetic proxies for ticagrelor exposure. Positive control analyses indicated that genetically surrogated serum ticagrelor levels (six SNPs) but not ARC levels (two SNPs) were significantly associated with lower risks of coronary heart disease. Therefore, the six SNPs were used as genetic instruments for ticagrelor exposure, and the genome-wide association study data for five infection outcomes were derived from the UK Biobank and FinnGen consortium. The two-sample MR analyses based on inverse variance-weighted methods indicated that genetic liability to ticagrelor exposure could reduce the risk of bacterial pneumonia (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.71-0.95, P = 8.75E-03) and sepsis (OR: 0.83, 95% CI: 0.73-0.94, P = 3.69E-03); however, no causal relationship between ticagrelor exposure and upper respiratory infection, pneumonia, and urinary tract infection was detected. Extensive sensitivity analyses corroborated these findings. Our MR study provides further evidence for the preventive effects of ticagrelor on bacterial pneumonia and sepsis.

The causal relationship between bacterial pneumonia and diabetes: a two-sample mendelian randomization study

ABSTRACT The escalating worldwide occurrence of diabetes mellitus, recognized as a chronic metabolic ailment contributing to an amplified global disease burden, has stimulated researchers to explore its etiology. Consequently, the study employed a two-sample Mendelian randomization (MR) methodology to examine the causal connection between bacterial pneumonia and diabetes, drawing upon the existing observational study that identified a potential association between bacterial pneumonia and diabetes. Furthermore, MR investigations suggest a reciprocal causal relationship between bacterial pneumonia and gestational diabetes mellitus(GDM), and a plausible causal link between bacterial pneumonia and T1DM. Background Previous observational studies have established the high prevalence of bacterial pneumonia in diabetic patients, which in turn leads to increased mortality. However, the presence of a causal connection between bacterial pneumonia and diabetes remains unobserved. Methods We chose genome-wide significant (Ρ < 1 × 10−5 and Ρ < 1 × 10−6) and independent (r2 < 0.001) single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to proceed a bidirectional two-sample MR study. The extracted SNPs explored the relationship between bacterial pneumonia and diabetes by Inverse variance weighted (IVW), MR-Egger, and weighted median methods. In addition, we conducted the Heterogeneity test, the Pleiotropy test, MR-presso and the Leave-one-out (LOO) sensitivity test to validate the reliability of results. Results In an MR study with bacterial pneumonia as an exposure factor, four different types of diabetes as outcome. It was observed that bacterial pneumonia increases the incidence of GDM (OR = 1.150 (1.027–1.274, P = 0.011) and T1DM (OR = 1.277 (1.024–1.531), P = 0.016). In the reverse MR analysis, it was observed that GDM (OR = 1.112 (1.023–1.201, P = 0.009) is associated with an elevated risk of bacterial pneumonia. However, no significant association was observed bacterial pneumonia with T1DM and other types of diabetes (P > 0.05). Conclusion This study utilizing MR methodology yields robust evidence supporting a bidirectional causal association between bacterial pneumonia and GDM. Furthermore, our findings suggest a plausible causal link between bacterial pneumonia and T1DM.

The Efficacy of High-Dose Pulse Therapy vs. Low-Dose Intravenous Methylprednisolone on Severe to Critical COVID-19 Clinical Outcomes: A Randomized Clinical Trial.

It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia. The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group). In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated. Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01). The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

Metformin use and the risk of bacterial pneumonia in patients with type 2 diabetes

Persons with type 2 diabetes (T2D) have neutrophil dysfunction with a higher risk of infection than those without diabetes. We conducted this study aiming to compare the risk of pneumonia between metformin use and nonuse in persons with T2D. We identified 49,012 propensity score-matched metformin users and nonusers from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2017. We used the Cox proportional hazards model to compare the risks of pneumonia and respiratory death. The mean (SD) age of the participants was 57.46 (12.88) years, and the mean follow-up time for metformin users and nonusers was 5.47 (3.71) years and 5.15 (3.87) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) for metformin use in bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death were 0.89 (0.84–0.94), 0.77 (0.73–0.82), and 0.64 (0.56–0.74), respectively. A longer cumulative duration of metformin use had further lower adjusted hazard ratios in these risks compared with nonuse. In patients with T2D, metformin use was associated with significantly lower risks of bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death; moreover, longer metformin use duration was associated with lower hazard ratios of these risks.

Factores relacionados con la neumonía bacteriana en pacientes con COVID-19 en una unidad de cuidados intensivos de Barranquilla, Colombia

ObjectiveTo determine the factors related to bacterial pneumonia in patients with COVID-19 in an intensive care unit in Barranquilla, Colombia. DesignNested, single-center case-control study, conducted between March and August 2020. PatientsPatients over 18 years of age, a hospital stay greater than 72h, with invasive mechanical ventilation support admitted to the intensive care unit. InterventionsNone. MeasurementsClinical variables were grouped for both cases and controls. Means and standard deviation were calculated in quantitative variables and proportions in categorical variables. Fisher's exact test was used to evaluate the differences between proportions, and the Mann-Whitney U test was used for differences in means. Variables with statistically significant differences were run in an explanatory model based on binary logistic regression. ResultsThe frequency of bacterial pneumonia was 10.07%, finding a high consumption of empirical antibiotic therapy. A statistical association was found between the time of dexamethasone use (OR 1.520; 95% CI 1.131-2.042) with the development of bacterial pneumonia. The rest of the variables were not statistically significant after adjusting the model with logistic regression. ConclusionLow rates of bacterial pneumonia were found, with Klebsiella pneumoniae prevailing as the most frequent bacterium. Overuse of dexamethasone in intensive care unit COVID-19 patients could increase the risk of bacterial pneumonia. For this reason, it must be evaluated in greater depth to explain causality and effect.

Association between Hydroxychloroquine and bacterial pneumonia in rheumatic patients: A population-based propensity score matching cohort study.

Whether hydroxychloroquine (HCQ) use could reduce lesser risk of bacterial infections is unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. The Longitudinal Health Insurance Database (LHID) from Taiwan National Health Insurance Research Database (NHIRD) of 23million Taiwanese populations was used. We included patients who were newly diagnosed with rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012. HCQ users and non-users were then matched according to age, sex, urbanisation level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulphate had no difference to that of patient without the use of HCQ sulphate in propensity score-matched cohort, (Log-rank test: P=.5). However, patients who used HCQ sulphate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ non-users as a reference. Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400days or lupus patients using HCQ was associated with lower risk of bacterial pneumonia.

Low vitamin D and risk of bacterial pneumonias: Mendelian randomisation studies in two population-based cohorts

BackgroundVitamin D may regulate the innate immune system, and randomised controlled trials suggest a beneficial effect of vitamin D supplementation against acute respiratory tract infections. By using a Mendelian randomisation...

Association between Hydroxychloroquine and Bacterial Pneumonia in Rheumatic Patients: A Population-Based Propensity Score Matching Cohort Study

Background: Association between hydroxychloroquine (HCQ) and bacterial infections required to be determined. Whether hydroxychloroquinehad use could reduce lesser risk of bacterial infections are unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. Methods: The Longitudinal Health Insurance Database (LHID), a one million extract from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who newly diagnosed rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012.HCQ users and nonusers were then matched according to age, sex, urbanization level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. Results: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulfate had no difference to that of patient without the use of HCQ sulfate in propensity score matched cohort, (Log-rank test: p-value=0.5). However, patients used HCQ sulfate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ nonusers as a reference. Conclusion: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days was associated with lower risk of bacteria pneumonia. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), China Medical University Hospital (CMU107-ASIA-19, DMR-109-231); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan. No additional external funding was received for this study. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the China Medical University Hospital (CMUH104-REC2-115(AR-4)).

Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial.

Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule. In a stepped-wedge cluster randomised trial, we included children aged 1-60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study. In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule. Netherlands Trial Register NTR5326.

2793. Influenza and Bacterial Pneumonia Coinfection: Rates and Outcomes

BackgroundLimited evidence suggests that influenza leads not only to bacterial colonization and greater risk of bacterial pneumonia, but to poor outcomes and increased mortality. We compared bacterial culture results between patients positive (FLU+) and negative (FLU-) for influenza in the setting of community-acquired pneumonia (CAP). Among FLU+ patients we compared bacterial etiology, characteristics, treatment and outcomes between patients with and without bacterial coinfection.MethodsWe included adults admitted with pneumonia 2010–2015 to 179 US hospitals participating in the Premier database. Pneumonia was identified using an ICD-9-CM algorithm. Among patients tested for FLU, we limited the microbiology results to the first 14 hospital days. We assessed inpatient mortality, ICU admission, use of vasopressors, mechanical ventilation (MV), cost, and LOS using mixed multiple logistic regression and gamma generalized linear mixed models.ResultsAmong 166,273 patients hospitalized with CAP, 38,665 (23.3%) were tested for influenza and 4,313 (11.15%) were positive. In FLU+ patients the most common bacterial co-infection was Staphylococcus aureus (37.6%) followed by Streptococcus pneumoniae (25.9%) and Pseudomonas aeruginosa (10.9%), varying based on the day of coinfection (days 1–3 vs. days 4–14) (Figure 1). In FLU- patients, S. pneumoniae (30.5%) and S. aureus (30.3%) were similarly common, followed by P. aeruginosa (10.0%). FLU+ patients with bacterial co-infection were younger (66.3 vs. 69.1 years), with more comorbidities (3.2 vs. 2.7) than influenza patients with no bacterial co-infection (all comparisons P < 0.001). Bacterial co-infection was also associated with increased odds of in-hospital mortality (OR 1.86, 95% CI,1.31–2.65), ICU admission (OR 3.46, 2.44–4.9), use of vasopressors (OR 3.74, 2.61–5.36), and MV (OR 3.51, 2.49–5.36), increased cost (risk-adjusted ratio of geometric means, 1.6, (1.47–1.73) and LOS (risk-adjusted ratio of geometric means 1.42, (1.33–1.52).ConclusionIn a large US inpatient sample hospitalized for CAP, 11% of patients with influenza had or acquired a bacterial co-infection. Bacterial co-infection was associated with significantly worse outcomes and higher cost. Disclosures All authors: No reported disclosures.

Utilidad de la proteína C reactiva sérica en el diagnóstico y tratamiento del adulto inmunocompetente hospitalizado por neumonía adquirida en la comunidad

C-reactive protein (CRP) is used to monitor patients' response during treatment of infectious diseases. Morbidity and mortality associated with community-acquired pneumonia (CAP) is high, particularly in hospitalized patients. Better risk prediction during hospitalization could improve management and ultimately reduce mortality rates. To evaluate CRP measured at admission and the third day of hospitalization as a predictor for adverse events in CAP. A prospective cohort study of adult patients hospitalized with CAP at an academic hospital. Major adverse outcomes were admission to ICU, mechanical ventilation, prolonged hospital length of stay, hospital complications and 30-day mortality. Predictive associations between CRP (as absolute levels and relative decline at third day) and adverse events were analyzed. Eight hundred and twenty-three patients were assessed, 19% were admitted to ICU and 10.6% required mechanical ventilation. The average hospital stay was 8.8 ± 8.2 days, 42% had nosocomial complications and 8.1% died within 30 days. Ninety eight percent of patients had elevated serum CRP on admission to the hospital (18.1 ± 14.1 mg/dL). C-reactive protein measured at admission was associated with the risk of bacterial pneumonia, bacteremic pneumonia, septic shock and use of mechanical ventilation. Lack of CRP decline within three days of hospitalization was associated with high risk of complications, septic shock, mechanical ventilation and prolonged hospital stay. CRP responses at third day of hospital admission was a valuable predictor of adverse events in hospitalized CAP adult patients.

Risk of bacterial pneumonia and pneumococcal infection in youths with celiac disease — A population-based study

ObjectiveAssess the risk of hospitalizations for bacterial pneumonia or pneumococcal infections, in a cohort of young individuals with celiac disease (CD) compared to matched references. Study designThe cohort consists of 213,635 individuals, born in 1989–2012 and resident in Friuli-Venezia Giulia (Italy). Through pathology reports, hospital discharge records or co-payment exemptions, we identified 1294 CD patients and 6470 reference individuals matched by gender and birth year. We considered hospital admissions for first episodes of bacterial pneumonia and pneumococcal infections. Hazard ratios (HRs) for episodes after CD diagnosis were calculated with Cox regression and odds ratios (OR) for the ones before CD diagnosis with conditional logistic regression. Further analyses were performed on unvaccinated follow-up periods. Results14 CD patients (in 9450 person-years) and 42 references (in 48,335 person-years) experienced a first episode of bacterial pneumonia, with an increased risk among CD patients (HR 1.82; 95%CI 0.98–3.35). Risks of bacterial pneumonia were significantly increased before CD diagnosis and especially the year before CD diagnosis (OR 6.00, 95%CI 1.83–19.66). Risks of pneumococcal infections showed a non-significant increase in CD patients. ConclusionsCD children and youth showed an increased risk of bacterial pneumonia, especially in proximity to CD diagnosis. Anti-pneumococcal vaccination should be recommended to all young CD patients.

Albumin-Bilirubin Score for Predicting Post-Transplant Complications Following Adult-to-Adult Living Donor Liver Transplantation.

BackgroundAlbumin-Bilirubin (ALBI) grade has been evaluated as an objective method to assess liver function and predict postoperative complications, particularly after hepatectomy in patients with hepatocellular carcinoma (HCC). However, ALBI grade was rarely used in evaluation in living donor liver transplantation (LDLT).Material/MethodsBetween March 2005 and November 2015, 272 consecutive patients undergoing right-lobe LDLT were enrolled in this study. According to the ALBI score used to evaluate recipients preoperatively, those patients were divided into 3 grades (I, II, and III). Demographic findings and the post-operative complication rates were collected and compared among groups.ResultsThe proportions of massive blood cell transfusions were different among those 3 grades (p<0.05). The patients in grade III had a higher risk of bacterial pneumonia and early allograft dysfunction (EAD) compared to grade I (p=0.029 and p=0.038, respectively) and grade II (p=0.006 and p=0.007, respectively). The area under the receiver operating characteristic curve of ALBI, Child-Pugh, and MELD for predicting 30-day mortality were 0.702 (95% CI: 0.644–0.756), 0.669 (95% CI: 0.580–0.697, p=0.510, versus ALBI grade), and 0.540 (95% CI: 0.580–0.697, p=0.144, versus ALBI grade), respectively.ConclusionsALBI grade was a good index for predicting post-operative complications and had a predictive ability similar to those of the Child-Pugh classification and MELD score.

Danger Signals from Influenza Infection Increase Risk of Bacterial Pneumonia

Danger Signals from Influenza Infection Increase Risk of Bacterial Pneumonia

Regulation of tracheal antimicrobial peptide gene expression in airway epithelial cells of cattle.

β-defensins are an important element of the mucosal innate immune response against bacterial pathogens. Tracheal antimicrobial peptide (TAP) has microbicidal activity against the bacteria that cause bovine respiratory disease, and its expression in tracheal epithelial cells is upregulated by bacterial products including lipopolysaccharide (LPS, a TLR4 agonist), Pam3CSK4 (an agonist of Toll-like receptor 2/1), and interleukin (IL)-17A. The objectives of this study were to identify the signalling pathway by which LPS, Pam3CSK4 and IL-17A induce TAP gene expression, and to determine the effect of glucocorticoid as a model of stress on this epithelial innate immune response. In primary cultures of bovine tracheal epithelial cells (bTEC), LPS, Pam3CSK4 and IL-17A each stimulated TAP gene expression. This effect was abrogated by caffeic acid phenylester (CAPE), an inhibitor of NF-κB. Similarly, western analysis showed that LPS, Pam3CSK4 and IL-17A each induced translocation of NF-κB p65 from the cytoplasm to the nucleus, but pre-treatment with CAPE inhibited this response. Finally, pre-treatment of bTEC with the glucocorticoid dexamethasone abolished the stimulatory effect of LPS, Pam3CSK4 and IL-17A on upregulation of TAP gene expression. These findings indicate that NF-κB activation is necessary for induction of TAP gene expression by LPS (a TLR4 agonist), Pam3CSK4 (a TLR2/1 agonist), or IL-17A. Furthermore, this stimulatory response is inhibited by glucocorticoid, suggesting this as one mechanism by which stress increases the risk of bacterial pneumonia. These findings have implications for understanding the pathogenesis of stress-associated bacterial pneumonia, and for developing methods to stimulate innate immune responses in the respiratory tract of cattle.

Airway Fungal Colonization Compromises the Immune System Allowing Bacterial Pneumonia to Prevail

To study the correlation between fungal colonization and bacterial pneumonia and to test the effect of antifungal treatments on the development of bacterial pneumonia in colonized rats. Experimental animal investigation. University research laboratory. Pathogen-free male Wistar rats weighing 250-275 g. Rats were colonized by intratracheal instillation of Candida albicans. Fungal clearance from the lungs and immune response were measured. Both colonized and noncolonized animals were secondarily instilled with different bacterial species (Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus aureus). Bacterial phagocytosis by alveolar macrophages was evaluated in the presence of interferon-gamma, the main cytokine produced during fungal colonization. The effect of antifungal treatments on fungal colonization and its immune response were assessed. The prevalence of P. aeruginosa pneumonia was compared in antifungal treated and control colonized rats. C. albicans was slowly cleared and induced a Th1-Th17 immune response with very high interferon-gamma concentrations. Airway fungal colonization favored the development of bacterial pneumonia. Interferon-gamma was able to inhibit the phagocytosis of unopsonized bacteria by alveolar macrophages. Antifungal treatment decreased airway fungal colonization, lung interferon-gamma levels and, consequently, the prevalence of subsequent bacterial pneumonia. C. albicans airway colonization elicited a Th1-Th17 immune response that favored the development of bacterial pneumonia via the inhibition of bacterial phagocytosis by alveolar macrophages. Antifungal treatment decreased the risk of bacterial pneumonia in colonized rats.