Community-Acquired Pneumonia in Children: Rapid Evidence Review.

In the United States, pneumonia is the most common cause of hospitalization in children. Even in hospitalized children, community-acquired pneumonia is most likely of viral etiology, with respiratory syncytial virus being the most common pathogen, especially in children younger than two years. Typical presenting signs and symptoms include tachypnea, cough, fever, and anorexia. Findings most strongly associated with an infiltrate on chest radiography in children with clinically suspected pneumonia are grunting, history of fever, retractions, crackles, tachypnea, and the overall clinical impression. Chest radiography should be ordered if the diagnosis is uncertain, if patients have hypoxemia or significant respiratory distress, or if patients fail to show clinical improvement within 48 to 72 hours after initiation of antibiotic therapy. Outpatient management of community-acquired pneumonia is appropriate in patients without respiratory distress who can tolerate oral antibiotics. Amoxicillin is the first-line antibiotic with coverage for Streptococcus pneumoniae for school-aged children, and treatment should not exceed seven days. Patients requiring hospitalization and empiric parenteral therapy should be transitioned to oral antibiotics once they are clinically improving and able to tolerate oral intake. Childhood and maternal immunizations against S. pneumoniae, Haemophilus influenzae type b, Bordetella pertussis, and influenza virus are the key to prevention.

Nasopharyngeal Carriage of Invasive Pneumococcal Serotypes During Childhood Community-Acquired Alveolar Pneumonia Is Associated With Specific Clinical Presentation.

BACKGROUND: Streptococcus pneumoniae (Pnc) serotypes differ in invasive potential. We examined whether community-acquired alveolar pneumonia (CAAP) in children carrying commonly recognized pneumonia invasive pneumococcal serotypes ([PnIST] 1, 5, 7F, 14, and 19A) differs from CAAP in children carrying less invasive serotypes (non-PnIST) or no Pnc (Pnc-neg). METHODS: Children <5 years, visiting the only regional Pediatric Emergency Room, with radiologically proven CAAP were enrolled. Nasopharyngeal cultures were processed for pneumococcal isolation and serotyping. Clinical and demographic characteristics were recorded. The study was conducted before pneumococcal conjugate vaccine implementation in Israel. RESULTS: A total of 1423 CAAP episodes were recorded: PnIST, 300 (21.1%); non-PnIST, 591 (41.5%); and Pnc-neg, 532 (37.4%). After adjustment for age, ethnicity, seasonality, and previous antibiotics, the following variables were positively associated with PnIST carriage compared with both groups: temperature ≥39°C, peripheral white blood cell count ≥20 000/mm3, C-reactive protein ≥70.0 mg/L, and serum sodium <135 mEq/L. Lower oxygen saturation, viral detection, and comorbidities were negatively associated with Pn-IST carriage (odds ratios, <1.0). Differences between non-PnIST carriers and Pnc-neg groups were smaller or nonsignificant. CONCLUSIONS: Young children with CAAP carrying common PnIST had a lower proportion of comorbidities, hypoxemia, and viral detection and had more intense systemic inflammatory response than those carrying non-PnIST or not carrying Pnc.

Neutrophils in community-acquired pneumonia: parallels in dysfunction at the extremes of age.

"Science means constantly walking a tight rope" Heinrich Rohrer, physicist, 1933. Community-acquired pneumonia (CAP) is the leading cause of death from infectious disease worldwide and disproportionately affects older adults and children. In high-income countries, pneumonia is one of the most common reasons for hospitalisation and (when recurrent) is associated with a risk of developing chronic pulmonary conditions in adulthood. Pneumococcal pneumonia is particularly prevalent in older adults, and here, pneumonia is still associated with significant mortality despite the widespread use of pneumococcal vaccination in middleand high-income countries and a low prevalence of resistant organisms. In older adults, 11% of pneumonia survivors are readmitted within months of discharge, often with a further pneumonia episode and with worse outcomes. In children, recurrent pneumonia occurs in approximately 10% of survivors and therefore is a significant cause of healthcare use. Current antibiotic trials focus on short-term outcomes and increasingly shorter courses of antibiotic therapy. However, the high requirement for further treatment for recurrent pneumonia questions the effectiveness of current strategies, and there is increasing global concern about our reliance on antibiotics to treat infections. Novel therapeutic targets and approaches are needed to improve outcomes. Neutrophils are the most abundant immune cell and among the first responders to infection. Appropriate neutrophil responses are crucial to host defence, as evidenced by the poor outcomes seen in neutropenia. Neutrophils from older adults appear to be dysfunctional, displaying a reduced ability to target infected or inflamed tissue, poor phagocytic responses and a reduced capacity to release neutrophil extracellular traps (NETs); this occurs in health, but responses are further diminished during infection and particularly during sepsis, where a reduced response to granulocyte colony-stimulating factor (G-CSF) inhibits the release of immature neutrophils from the bone marrow. Of note, neutrophil responses are similar in preterm infants. Here, the storage pool is decreased, neutrophils are less able to degranulate, have a reduced migratory capacity and are less able to release NETs. Less is known about neutrophil function from older children, but theoretically, impaired functions might increase susceptibility to infections. Targeting these blunted responses may offer a new paradigm for treating CAP, but modifying neutrophil behaviour is challenging; reducing their numbers or inhibiting their function is associated with poor clinical outcomes from infection. Uncontrolled activation and degranulation can cause significant host tissue damage. Any neutrophil-based intervention must walk the tightrope described by Heinrich Rohrer, facilitating necessary phagocytic functions while preventing bystander host damage, and this is a significant challenge which this review will explore.

Risk factors and clinical characteristics of patients with nosocomial influenza A infection.

Influenza is a public health burden, responsible for more than half a million deaths worldwide each year and explosive outbreaks in-hospital care units. At present, little is known about clinical characteristics and outcomes with nosocomial influenza infection. To assess clinical characteristics and outcome between nosocomial and community-acquired (CA) influenza in a tertiary care hospital. A retrospective study of hospitalized patients in a French tertiary care hospital from 1st December 2016 to 28th February 2017 for flu-illness confirmed by reverse transcription PCR. Overall, 208 patients with laboratory-confirmed influenza were included; whose 49 nosocomial cases (23.6%). Patients with nosocomial influenza were significantly older (79.1 ± 15.5 vs 64.8 ± 31.1 years old; P = .003), with the more rapidly fatal disease (10.2% vs 1.3%; P = .0032). They had a less respiratory failure (8.2% vs 21.4%; P = .036) but had a longer length of hospitalization (47.3 vs 12.9 days; P < .001) than patients with CA influenza. During this influenza outbreak, 19 patients died (9.1%), none of them were vaccinated. Effective control of outbreaks in hospital facilities is challenging. Hospitalized patients are vulnerable to nosocomial Influenza infections that can increase the length of stay and be responsible for the death. Surveillance and early warning systems should be encouraged. Vaccination policies in conjunction with isolation measures and better hand hygiene could reduce virus spreading in hospitals.

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis.

BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

Presence of urinary symptoms in bacteremic urinary tract infection: a retrospective cohort study of Escherichia coli bacteremia.

BACKGROUND: It is important to understand clinical features of bacteremic urinary tract infection (bUTI), because bUTI is a serious infection that requires prompt diagnosis and antibiotic therapy. Escherichia coli is the most common and important uropathogen. The objective of our study was to characterize the clinical presentation of E coli bUTI. METHODS: Retrospective cohort study of consecutive adult patients admitted for community acquired E. coli bacteremia from January 1, 2015 to December 31, 2016 was conducted at 4 acute care academic and community hospitals in Toronto, Ontario, Canada. Logistic regression models were developed to identify E coli bUTI cases without urinary symptoms. RESULTS: Of 462 patients with E. coli bacteremia, 284 (61.5%) patients had a urinary source. Of these 284 patients, 161 (56.7%) had urinary symptoms. In a multivariable model, bUTI without urinary symptoms were associated with older age (age < 65 years as reference, age 65-74 years had OR of 2.13 95% CI 0.99-4.59 p = 0.0523; age 75-84 years had OR of 1.80 95% CI 0.91-3.57 p = 0.0914; age > =85 years had OR of 2.95 95% CI 1.44-6.18 p = 0.0036) and delirium (OR of 2.12 95% CI 1.13-4.03 p = 0.0207). Sepsis by SIRS criteria was present in 274 (96.5%) of all bUTI cases and 119 (96.8%) of bUTI cases without urinary symptoms. CONCLUSION: The majority of patients with E. coli bacteremia had a urinary source. A significant proportion of bUTI cases had no urinary symptoms elicited on history. Elderly and delirious patients were more likely to have bUTI without urinary symptoms. In elderly and delirious patients with sepsis by SIRS criteria but without a clear infectious source, clinicians should suspect, investigate, and treat for bUTI.

Serum Prealbumin Improves the Sensitivity of Pneumonia Severity Index in Predicting 30-day Mortality of CAP Patients.

BACKGROUND: Serum prealbumin (PAB) is an effective tool to evaluate patients with malnutrition. In recent years, studies have shown that PAB is statistically reduced during the course of disease infection. The pneumonia severity index (PSI) scoring system is one of the most widely used scoring tools to evaluate the condition and prognosis of community acquired pneumonia (CAP) patients. However, few studies have reported on PSI combined with blood indicators to predict the prognosis of pneumonia. The aim of this study was to investigate the prognostic value of PAB combined with PSI in patients with CAP. METHODS: We retrospectively analyzed the data of 400 patients who met the inclusion criteria. Death and survival were selected as prognostic indicators of pneumonia. On the first day after admission, venous blood samples were taken to test PAB and PSI scores. Subject operating characteristic curve (ROC) was used to evaluate PSI, PAB, and PSI combined with PAB to predict 30-day mortality of CAP patients. RESULTS: The 30-day mortality rate of CAP patients was 10.5% (42/400). PAB and PSI score were independent risk factors for 30-day mortality in CAP patients. The sensitivity, specificity, positive predictive value, and negative predictive value of PAB predicting the death of CAP patients were 86.3%, 79%, 50.74%, and 95.83%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of PSI predicting the death of CAP patients were 74.80%, 63%, 33.71%, and 90.99%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the combined index predicting the death of CAP patients were 95.20%, 77.80%, 51.70% and 98.41%, respectively. CONCLUSIONS: Serum prealbumin is a relatively simple acquired index and an independent risk factor for death in CAP patients. Serum prealbumin improves the sensitivity of pneumonia severity index in predicting 30-day mortality of CAP patients.

Community-acquired Respiratory Viruses Are a Risk Factor for Chronic Lung Allograft Dysfunction.

BACKGROUND: The relationship between community-acquired respiratory viruses (CARVs) and chronic lung allograft dysfunction (CLAD) in lung transplant recipients is still controversial. METHODS: We performed a prospective cohort study (2009-2014) in all consecutive adult patients (≥18 years) undergoing lung transplantation in the Hospital Universitari Vall d'Hebron (Barcelona, Spain). We systematically collected nasopharyngeal swabs from asymptomatic patients during seasonal changes, from patients with upper respiratory tract infectious disease, lower respiratory tract infectious disease (LRTID), or acute rejection. Nasopharyngeal swabs were analyzed by multiplex polymerase chain reaction. Primary outcome was to evaluate the potential association of CARVs and development of CLAD. Time-dependent Cox regression models were performed to identify the independent risk factors for CLAD. RESULTS: Overall, 98 patients (67 bilateral lung transplant recipients; 63.3% male; mean age, 49.9 years) were included. Mean postoperative follow-up was 3.4 years (interquartile range [IQR], 2.5-4.0 years). Thirty-eight lung transplant recipients (38.8%) developed CLAD, in a median time of 20.4 months (IQR, 12-30.4 months). In time-controlled multivariate analysis, CARV-LRTID (hazard ratio [HR], 3.00 [95% confidence interval {CI}, 1.52-5.91]; P = .002), acute rejection (HR, 2.97 [95% CI, 1.51-5.83]; P = .002), and cytomegalovirus pneumonitis (HR, 3.76 [95% CI, 1.23-11.49]; P = .02) were independent risk factors associated with developing CLAD. CONCLUSIONS: Lung transplant recipients with CARVs in the lower respiratory tract are at increased risk to develop CLAD.

Chronic alcohol abuse affects the clinical course and outcome of community-acquired bacterial meningitis.

The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (p < 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (p = 0.002) and lower on the Glasgow Coma Scale (GCS) (p < 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (p < 0.001). Furthermore, alcoholics were less likely to complain of headache (p < 0.001) and nausea/vomiting (p = 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (p = 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (p = 0.036), presence of seizures (p = 0.041), male gender (p = 0.042), and absence of nausea/vomiting (p = 0.040). Furthermore, alcoholism (p = 0.031), lower GCS score (p = 0.001), and higher blood urea concentration (p = 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.

Multidrug Resistant Gram-Negative Bacteria in Community-Acquired Pneumonia.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

The Relationship of Paranasal Sinus Opacification to Hospital-Acquired Pneumonia in the Neurologic Intensive Care Unit Patient.

BACKGROUND: The association between intensive care unit (ICU) sinusitis and the development of lower airway infections remains unclear. The objective of this study was to determine the correlation between the development of radiographic sinus opacification and pneumonia in the neurologic ICU setting. METHODS: A retrospective review of head computed tomography or magnetic resonance imaging of 612 patients admitted to the neurocritical care unit at a tertiary care center from April 2013 through April 2014 was performed. Paranasal sinus opacification was measured using Lund-Mackay scores (LMS). A diagnosis of pneumonia was determined by the ICU team from radiographic, laboratory, and pulmonary data. Exclusion criteria included a history of endonasal surgery, sinonasal malignancy, facial fractures, ICU admission less than 3 days, or inadequate imaging. RESULTS: Worsening sinus opacification occurred in 42.6% of patients and pneumonia in 18.5% of patients during ICU admission. Of the patients who developed pneumonia, 71.7% also developed worsening sinus opacification (P < .001). In 80.2% of cases, the sinus opacification developed prior to the diagnosis of pneumonia. The mean highest LMS for patients who developed pneumonia was 4.24 compared to 1.99 in patients who did not develop pneumonia (P < .001). Sinus air-fluid levels or complete sinus opacification occurred in a larger proportion of patients who developed pneumonia (46.9% vs 19.4%, P < .001). Mortality rates for patients with no pneumonia or sinusitis, pneumonia only, sinusitis only, and sinusitis with pneumonia were 7.6%, 15.6%, 18.3%, and 25.9%, respectively (P < .001). CONCLUSIONS: This study finds a strong relationship between worsening sinus opacification in the neurologic ICU patient to the development of hospital-acquired pneumonia and increased mortality.

Initial Inflammatory Profile in Community-acquired Pneumonia Depends on Time since Onset of Symptoms.

RATIONALE: Assessment of the inflammatory response can help the decision-making process when diagnosing community-acquired pneumonia (CAP), but there is a lack of information about the influence of time since onset of symptoms. OBJECTIVES: We studied the impact of the number of days since onset of symptoms on inflammatory cytokines and biomarker concentrations at CAP diagnosis in hospitalized patients. METHODS: We performed a secondary analysis in two prospective cohorts including 541 patients in the derivation cohort and 422 in the validation cohort. The time since onset of symptoms was self-reported, and patients were classified as early presenters (<3 d) and nonearly presenters. Biomarkers (C-reactive protein [CRP] and procalcitonin [PCT] in both cohorts) and cytokines in the derivation cohort (IL-1, - 6, -8, -10, and tumor necrosis factor-α) were measured within 24 hours of hospital admission. MEASUREMENTS AND MAIN RESULTS: In early presenters, CRP was significantly lower, whereas PCT, IL-6, and IL-8 were higher. Nonearly presenters showed significantly lower PCT, IL-6, and IL-8 levels. In the validation cohort, CRP and PCT exhibited identical patterns: CRP levels were 36.4% greater in patients with 3 or more days since onset of symptoms than in those with less than 3 days since symptom onset in the derivation cohort and 38.2% in the validation cohort. PCT levels were 40% lower in patients with 3 or more days since onset of symptoms in the derivation cohort and 56% in the validation cohort. CONCLUSIONS: Time since symptom onset modifies the systemic inflammatory profile at CAP diagnosis. This information has relevant clinical implications for management, and it should be taken into account in the design of future clinical trials.

Dynamic thiol/disulfide homeostasis in children with community-acquired pneumonia.

BACKGROUND: Alteration in thiol level under oxidative stress may contribute to community-acquired pneumonia (CAP). The goal of this study was to determine whether there are changes in thiol/disulfide homeostasis and nitric oxide (NO) in children with CAP. METHODS: In total, 130 participants were involved in the study. Of these, 65 had been diagnosed with CAP on admission, and the remaining 65 were healthy individuals. Serum total thiol and native thiol were measured in each participant using a novel automated spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. Serum NO was measured on chemiluminescence assay. RESULTS: Average native thiol, total thiol, and disulfide in the CAP group were significantly lower than in the healthy individuals (P < 0.0001, P < 0.0001, P = 0.0126, respectively). In addition, disulfide/native thiol (P = 0.0002), and disulfide/total thiol ratios (P = 0.0004) were significantly higher, whereas the native thiol/total thiol ratio (P = 0.0004) was lower in the CAP group. High serum NO was noted in the CAP group (P = 0.0003), but there was no marked correlation between thiol/disulfide and NO. CONCLUSION: The changes in endogenous thiol levels under oxidative stress may be associated with the pathogenesis of CAP in pediatric patients.

Metabolic profiles in community-acquired pneumonia: developing assessment tools for disease severity.

BACKGROUND: This study aimed to determine whether community-acquired pneumonia (CAP) had a metabolic profile and whether this profile can be used for disease severity assessment. METHODS: A total of 175 individuals including 119 CAP patients and 56 controls were enrolled and divided into two cohorts. Serum samples from a discovery cohort (n = 102, including 38 non-severe CAP, 30 severe CAP, and 34 age and sex-matched controls) were determined by untargeted ultra-high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics. Selected differential metabolites between CAP patients versus controls, and between the severe CAP group versus non-severe CAP group, were confirmed by targeted mass spectrometry assays in a validation cohort (n = 73, including 32 non-severe CAP, 19 severe CAP and 22 controls). Pearson's correlation analysis was performed to assess relationships between the identified metabolites and clinical severity of CAP. The area under the curve (AUC), sensitivity and specificity of the metabolites for predicting the severity of CAP were also investigated. RESULTS: The metabolic signature was markedly different between CAP patients and controls. Fifteen metabolites were found to be significantly dysregulated in CAP patients, which were mainly mapped to the metabolic pathways of sphingolipid, arginine, pyruvate and inositol phosphate. The alternation trends of five metabolites among the three groups including sphinganine, p-Cresol sulfate, dehydroepiandrosterone sulfate (DHEA-S), lactate and L-arginine in the validation cohort were consistent with those in the discovery cohort. Significantly lower concentrations of sphinganine, p-Cresol sulfate and DHEA-S were observed in CAP patients than in controls (p < 0.05). Serum lactate and sphinganine levels were positively correlated with confusion, urea level, respiratory rate, blood pressure, and age > 65 years (CURB-65), pneumonia severity index (PSI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, while DHEA-S inversely correlated with the three scoring systems. Combining lactate, sphinganine and DHEA-S as a metabolite panel for discriminating severe CAP from non-severe CAP exhibited a better AUC of 0.911 (95% confidence interval 0.825-0.998) than CURB-65, PSI and APACHE II scores. CONCLUSIONS: This study demonstrates that serum metabolomics approaches based on the LC-MS/MS platform can be applied as a tool to reveal metabolic changes during CAP and establish a metabolite signature related to disease severity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03093220 . Registered retrospectively on 28 March 2017.

CURB-65 Score is Equal to NEWS for Identifying Mortality Risk of Pneumonia Patients: An Observational Study.

IMPORTANCE: The CURB-65 score is widely implemented as a prediction tool for identifying patients with community-acquired pneumonia (cap) at increased risk of 30-day mortality. However, since most ingredients of CURB-65 are used as general prediction tools, it is likely that other prediction tools, e.g. the British National Early Warning Score (NEWS), could be as good as CURB-65 at predicting the fate of CAP patients. OBJECTIVE: To determine whether NEWS is better than CURB-65 at predicting 30-day mortality of CAP patients. DESIGN: This was a single-centre, 6-month observational study using patients' vital signs and demographic information registered upon admission, survival status extracted from the Danish Civil Registration System after discharge and blood test results extracted from a local database. SETTING: The study was conducted in the medical admission unit (MAU) at the Hospital of South West Jutland, a regional teaching hospital in Denmark. PARTICIPANTS: The participants consisted of 570 CAP patients, 291 female and 279 male, median age 74 (20-102) years. RESULTS: The CURB-65 score had a discriminatory power of 0.728 (0.667-0.789) and NEWS 0.710 (0.645-0.775), both with good calibration and no statistical significant difference. CONCLUSION: CURB-65 was not demonstrated to be significantly statistically better than NEWS at identifying CAP patients at risk of 30-day mortality.

Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

RATIONALE: Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. OBJECTIVES: We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. METHODS: Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. MEASUREMENTS AND MAIN RESULTS: Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. CONCLUSIONS: These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

Changes in pulmonary artery systolic pressure correlate with radiographic severity and peripheral oxygenation in adults with community-acquired pneumonia.

PURPOSE: The aim of this prospective observational study was to evaluate the relationship between changes in pulmonary artery systolic pressure (ΔPASP) and both severity of community-acquired pneumonia (CAP) and changes in peripheral blood oxygen partial pressure (PaO2 ). MATERIALS AND METHODS: Seventy-five consecutive adult patients hospitalized for treatment of CAP were recruited in this single-center cohort study. Doppler echocardiographic measurement of PASP was performed by 2 staff cardiologists. Follow-up assessment was performed within 2 to 4 weeks of ending antibiotic treatment at radiographic resolution of CAP. Fifteen patients were excluded during follow-up due to confirmation of chronic obstructive pulmonary disease. RESULTS: Pneumonia was unilateral in 40 (66.7%) and bilateral in 20 (33.3%) patients. Radiographic extent of pneumonia involved 2 pulmonary segments in 31 patients (51.7%), 3 to 5 pulmonary segments in 25 (41.7%), and 6 pulmonary segments in 4 patients (6.6%). ΔPASP between hospital admission and follow-up correlated with the number of pulmonary segments involved (Rho = 0.953; P < .001) and PaO2 (Rho = -0.667; P < .001). The maximum PASP was greater during pneumonia than after resolution (34.82 ± 3.96 vs. 22.67 ± 4.04, P < .001). CONCLUSIONS: Changes in PASP strongly correlated with radiological severity of CAP and PaO2 . During pneumonia, PASP appeared increased without significant change in left ventricular filling pressures. This suggests that disease-related changes in lung tissue caused by pneumonia may easily and reproducibly be assessed using conventional noninvasive bedside diagnostics such as echocardiography and arterial blood gas analysis.

[ABNORMALITIES OF THYROID HORMONE METABOLISM DURING COMMUNITY‒ACQUIRED PNEUMONIA: NONTHYROIDAL ILLNESS SYNDROME AND INTRACELLULAR IODINE DISTRIBUTION IN CHILDREN].

The aim of the study ‒ to investigate the changes of thyroid function and to reveal the relationship in between intracellular distribution of iodine in the blood with the severity of the course of pneumonia in children. We investigated 70 patients in age 6-14 years with moderate and severe CAP and 35 healthy children. The levels of free thyroxine (fT4), free triiodo-thyronine (fT3) and thyroid stimulating hormone, thyroid gland ultrasound and urinary iodine were estimated. Inorganic iodine, total and organificated iodine was investigated. The article presents that severe pneumonia in children is characterized by a transient low level of fT3 2,89 pmol/L (p˂0,05). In a dynamics initially low levels of fT3 raise up to normal data. The general condition and clinical symptoms of the patients was improving after treatment of pneumonia and thyroid status was normalized. Mild iodine deficiency has been established in all children. The intracellular pool of iodine with severe pneumonia showed an inverse relationship between the levels of iodine distribution for organificated and inorganic iodine and a close connection between the levels of total and organic iodine (p<0,001). Nonthyroid illness syndrome developed for patients with severe community-acquired pneumonia. The revealed changes in indices of the intracellular pool of iodine and its distribution in the body are directly proportional to the severity of CAP.

A longitudinal modelling study estimates acute symptoms of community acquired pneumonia recover to baseline by 10†days.

Our aims were to address three fundamental questions relating to the symptoms of community-acquired pneumonia (CAP): Do patients completely recover from pneumonia symptoms? How long does this recovery take? Which factors influence symptomatic recovery?We prospectively recruited patients at two hospitals in Liverpool, UK, into a longitudinal, observational cohort study and modelled symptom recovery from CAP. We excluded patients with cancer, immunosuppression or advanced dementia, and those who were intubated or palliated from admission. We derived a statistical model to describe symptom patterns.We recruited 169 (52% male) adults. Multivariable analysis demonstrated that the time taken to recover to baseline was determined by the initial severity of symptoms. Severity of symptoms was associated with comorbidity and was inversely related to age. The pattern of symptom recovery was exponential and most patients' symptoms returned to baseline by 10 days.These results will inform the advice given to patients regarding the resolution of their symptoms. The recovery model described here will facilitate the use of symptom recovery as an outcome measure in future clinical trials.

Functional status and mortality prediction in community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Poor functional status (FS) has been suggested as a poor prognostic factor in both pneumonia and severe pneumonia in elderly patients. However, it is still unclear whether FS is associated with outcomes and improves survival prediction in community-acquired pneumonia (CAP) in the general population. METHODS: Data on hospitalized patients with CAP and FS, assessed by the Eastern Cooperative Oncology Group (ECOG) scale were prospectively collected between January 2008 and December 2012. The independent association of FS with 30-day mortality in CAP patients was evaluated using multivariable logistic regression. Improvement in mortality prediction when FS was added to the CRB-65 (confusion, respiratory rate, blood pressure and age 65) score was evaluated for discrimination, reclassification and calibration. RESULTS: The 30-day mortality of study participants (n = 1526) was 10%. Mortality significantly increased with higher ECOG score (P for trend <0.001). In multivariable analysis, ECOG ≥3 was strongly associated with 30-day mortality (adjusted OR: 5.70; 95% CI: 3.82-8.50). Adding ECOG ≥3 significantly improved the discriminatory power of CRB-65. Reclassification indices also confirmed the improvement in discrimination ability when FS was combined with the CRB-65, with a categorized net reclassification index (NRI) of 0.561 (0.437-0.686), a continuous NRI of 0.858 (0.696-1.019) and a relative integrated discrimination improvement in the discrimination slope of 139.8 % (110.8-154.6). CONCLUSION: FS predicted 30-day mortality and improved discrimination and reclassification in consecutive CAP patients. Assessment of premorbid FS should be considered in mortality prediction in patients with CAP.