Christopher Trabue

Differential regulation of SOCS-1 signalling in B and T lymphocytes by hepatitis C virus core protein.

Hepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T‐cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core–gC1qR interaction, with down‐regulation of CD69 activation in T cells but up‐regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon‐γ production in CD8+ T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7‐2), CD154 (CD40L) and CD195 (CCR5), in CD20+ B cells. Finally, we showed down‐regulation of suppressor of cytokine signalling‐1 (SOCS‐1) using real‐time reverse transcription–polymerase chain reaction, accompanied by up‐regulation of signal transducer and activator of transcription‐1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core‐treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.

Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes

Despite low prevalence of methicillin-resistant Staphylococcus aureus (MRSA; 0.7%), nearly one-third of adults hospitalized with community-acquired pneumonia (CAP) received anti-MRSA antibiotics. Characteristics of MRSA and pneumococcal CAP overlapped substantially, highlighting the challenge of accurately targeting anti-MRSA antibiotics using clinical criteria.

Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia

Summary Recent trials suggest procalcitonin-based guidelines can reduce antibiotic use for respiratory infections. However, the accuracy of procalcitonin to discriminate between viral and bacterial pneumonia requires further dissection.

Hepatitis C: the complications of immune dysfunction.

Hepatitis C virus (HCV) infection has been linked to numerous diseases of immune dysfunction, including, but not limited to, essential mixed cryoglobulinemia and non-Hodgkin’s lymphoma. Clinical studies support these associations and treatment of the underlying HCV infection has been variably successful. Recent studies, focusing on the role of HCV gene products, have discovered evidence of dysregulated responses in multiple aspects of host immunity that may be contributing to the genesis of these diseases. Novel treatments that target these areas of dysregulation offer hope for improved therapy for the diseases associated with immunodysregulation by HCV.

Statin Use and Hospital Length of Stay Among Adults Hospitalized With Community-acquired Pneumonia

BACKGROUND Prior retrospective studies suggest that statins may benefit patients with community-acquired pneumonia (CAP) due to antiinflammatory and immunomodulatory effects. However, prospective studies of the impact of statins on CAP outcomes are needed. We determined whether statin use was associated with improved outcomes in adults hospitalized with CAP. METHODS Adults aged ≥18 years hospitalized with CAP were prospectively enrolled at 3 hospitals in Chicago, Illinois, and 2 hospitals in Nashville, Tennessee, from January 2010-June 2012. Adults receiving statins before and throughout hospitalization (statin users) were compared with those who did not receive statins (nonusers). Proportional subdistribution hazards models were used to examine the association between statin use and hospital length of stay (LOS). In-hospital mortality was a secondary outcome. We also compared groups matched on propensity score. RESULTS Of 2016 adults enrolled, 483 (24%) were statin users; 1533 (76%) were nonusers. Statin users were significantly older, had more comorbidities, had more years of education, and were more likely to have health insurance than nonusers. Multivariable regression demonstrated that statin users and nonusers had similar LOS (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], .88-1.12), as did those in the propensity-matched groups (HR, 1.03; 95% CI, .88-1.21). No significant associations were found between statin use and LOS or in-hospital mortality, even when stratified by pneumonia severity. CONCLUSIONS In a large prospective study of adults hospitalized with CAP, we found no evidence to suggest that statin use before and during hospitalization improved LOS or in-hospital mortality.

Improved Detection of Respiratory Pathogens by Use of High-Quality Sputum with TaqMan Array Card Technology.

ABSTRACT New diagnostic platforms often use nasopharyngeal or oropharyngeal (NP/OP) swabs for pathogen detection for patients hospitalized with community-acquired pneumonia (CAP). We applied multipathogen testing to high-quality sputum specimens to determine if more pathogens can be identified relative to NP/OP swabs. Children (<18 years old) and adults hospitalized with CAP were enrolled over 2.5 years through the Etiology of Pneumonia in the Community (EPIC) study. NP/OP specimens with matching high-quality sputum (defined as ≤10 epithelial cells/low-power field [lpf] and ≥25 white blood cells/lpf or a quality score [q-score] definition of 2+) were tested by TaqMan array card (TAC), a multipathogen real-time PCR detection platform. Among 236 patients with matched specimens, a higher proportion of sputum specimens had ≥1 pathogen detected compared with NP/OP specimens in children (93% versus 68%; P < 0.0001) and adults (88% versus 61%; P < 0.0001); for each pathogen targeted, crossing threshold (CT) values were earlier in sputum. Both bacterial (361 versus 294) and viral detections (245 versus 140) were more common in sputum versus NP/OP specimens, respectively, in both children and adults. When available, high-quality sputum may be useful for testing in hospitalized CAP patients.

In-hospital Pneumococcal Polysaccharide Vaccination is Associated with Detection of Pneumococcal Vaccine Serotypes in Adults Hospitalized for Community-acquired Pneumonia

During an etiology study of adults hospitalized for pneumonia, in which urine specimens were examined for serotype-specific pneumococcal antigen detection, we observed that some patients received 23-valent pneumococcal polysaccharide vaccine before urine collection. Some urine samples became positive for specific vaccine pneumococcal serotypes shortly after vaccination, suggesting false-positive test results.

Fusobacterium nucleatum prosthetic hip infection in an adult with sickle cell-beta thalassemia

Fusobacterium nucleatum is an anaerobic Gram-negative bacillus commensal to the human oropharynx and gastrointestinal tract which causes an array of human infection, yet it has never been associated with infection of prosthetic joints. We report the first case of prosthetic hip infection caused by F. nucleatum in a man with sickle cell-beta thalassemia.

Perinatal Sepsis Caused by Williamsia serinedens Infection in a 31-Year-Old Pregnant Woman

ABSTRACT Williamsia serinedens has been isolated from soil but has not yet been implicated in human disease. We report the first case of perinatal sepsis caused by a dual-morphotype form of Williamsia serinedens in a 31-year-old pregnant woman hospitalized with preterm labor.

Relationship Between Body Mass Index and Outcomes Among Hospitalized Patients With Community-Acquired Pneumonia

Background The effect of body mass index (BMI) on community-acquired pneumonia (CAP) severity is unclear. Methods We investigated the relationship between BMI and CAP outcomes (hospital length of stay [LOS], intensive care unit [ICU] admission, and invasive mechanical ventilation) in hospitalized CAP patients from the Centers for Disease Control and Prevention Etiology of Pneumonia in the Community (EPIC) study, adjusting for age, demographics, underlying conditions, and smoking status (adults only). Results Compared with normal-weight children, odds of ICU admission were higher in children who were overweight (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.1-2.8) or obese (aOR, 2.1; 95% CI, 1.4-3.2), and odds of mechanical ventilation were higher in children with obesity (aOR, 2.7; 95% CI, 1.3-5.6). When stratified by asthma (presence/absence), these findings remained significant only in children with asthma. Compared with normal-weight adults, odds of LOS >3 days were higher in adults who were underweight (aOR, 1.6; 95% CI, 1.1-2.4), and odds of mechanical ventilation were lowest in adults who were overweight (aOR, 0.5; 95% CI, .3-.9). Conclusions Children who were overweight or obese, particularly those with asthma, had higher odds of ICU admission or mechanical ventilation. In contrast, adults who were underweight had longer LOS. These results underscore the complex relationship between BMI and CAP outcomes.