Longitudinal Study of the Effects of Bacteremia and Sepsis on 5-year Risk of Cardiovascular Events.

BACKGROUND: The long-term and cumulative effect of multiple episodes of bacteremia and sepsis across multiple hospitalizations on the development of cardiovascular (CV) events is uncertain. METHODS: We conducted a longitudinal study of 156 380 hospitalizations in 47 009 patients (≥18 years old) who had at least 2 inpatient admissions at an academic tertiary care center in St Louis, Missouri, from 1 January 2008 through 31 December 2012. We used marginal structural models, estimated by inverse probability weighting (IPW) of bacteremia or sepsis and IPW of censoring, to estimate the marginal causal effects of bacteremia and sepsis on developing the first observed incident CV event, including stroke, transient ischemic attack, and myocardial infarction (MI), during the study period. RESULTS: Bacteremia and sepsis occurred during 4923 (3.1%) and 5544 (3.5%) hospitalizations among 3932 (8.4%) and 4474 (9.5%) patients, respectively. CV events occurred in 414 (10.5%) and 538 (12.0%) patients with prior episodes of bacteremia or sepsis, respectively, vs 3087 (7.2%) and 2963 (7.0%) patients without prior episodes of bacteremia or sepsis. The causal odds of experiencing a CV event was 1.52-fold (95% confidence interval [CI], 1.21- to 1.90-fold) and 2.39-fold (95% CI, 1.88- to 3.03-fold) higher in patients with prior instances of bacteremia or sepsis, respectively, compared to those without. Prior instances of septic shock resulted in a 6.91-fold (95% CI, 5.34- to 8.93-fold) increase in the odds of MI. CONCLUSIONS: Prior instances of bacteremia and sepsis substantially increase the 5-year risk of CV events.

Aquatic surface respiration and swimming behaviour in adult and developing zebrafish exposed to hypoxia.

Severe hypoxia elicits aquatic surface respiration (ASR) behaviour in many species of fish, where ventilation of the gills at the air-water interface improves O2 uptake and survival. ASR is an important adaptation that may have given rise to air breathing in vertebrates. The neural substrate of this behaviour, however, is not defined. We characterized ASR in developing and adult zebrafish (Danio rerio) to ascertain a potential role for peripheral chemoreceptors in initiation or modulation of this response. Adult zebrafish exposed to acute, progressive hypoxia (PO2 from 158 to 15 mmHg) performed ASR with a threshold of 30 mmHg, and spent more time at the surface as PO2 decreased. Acclimation to hypoxia attenuated ASR responses. In larvae, ASR behaviour was observed between 5 and 21 days postfertilization with a threshold of 16 mmHg. Zebrafish decreased swimming behaviour (i.e. distance, velocity and acceleration) as PO2 was decreased, with a secondary increase in behaviour near or below threshold PO2 . In adults that underwent a 10-day intraperitoneal injection regime of 10 µg g(-1) serotonin (5-HT) or 20 µg g(-1) acetylcholine (ACh), an acute bout of hypoxia (15 mmHg) increased the time engaged in ASR by 5.5 and 4.9 times, respectively, compared with controls. Larvae previously immersed in 10 µmol l(-1) 5-HT or ACh also displayed an increased ASR response. Our results support the notion that ASR is a behavioural response that is reliant upon input from peripheral O2 chemoreceptors. We discuss implications for the role of chemoreceptors in the evolution of air breathing.

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

BACKGROUND: Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. METHODS: We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. RESULTS: We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. CONCLUSIONS: The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop strategies to integrate clinical patient-level data with administrative data to draw more accurate conclusions about the epidemiology of sepsis.

Routine testing for anaerobic bacteria in cerebrospinal fluid cultures improves recovery of clinically significant pathogens.

In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens.

De Novo meningitis caused by Propionibacterium acnes in a patient with metastatic melanoma.

Propionibacterium acnes is a known cause of postneurosurgical meningitis; however, it is rarely implicated in de novo meningitis. Herein we report a case of a 49-year-old male with de novo meningitis caused by P. acnes with metastatic melanoma as the only identified risk factor for his infection.

A Lethal Case of Pseudomonas putida Bacteremia Due to Soft Tissue Infection.

Pseudomonas putida is an uncommon cause of skin and soft tissue infections. It is often associated with trauma or immunocompromised state. We present the first lethal case of bacteremia due to skin and soft tissue infections, which had malnutrition, immobility, and peripheral vascular disease as risk factors.

Native valve Bacillus cereus endocarditis in a non-intravenous-drug-abusing patient.

Bacillus cereus is a rare cause of endocarditis, typically associated with intravenous drug abuse, rheumatic heart disease, prosthetic heart valves, pacemakers, or immunodeficiency. We present the first case of native valve Bacillus cereus endocarditis with no apparent risk factors. The patient had a fulminant course requiring emergent valve replacement.

Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

PURPOSE: To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. METHODS: We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. RESULTS: When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. CONCLUSIONS: Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence.

Sepsis surveillance from administrative data in the absence of a perfect verification.

PURPOSE: Past studies of sepsis epidemiology did not address misclassification bias due to imperfect verification of sepsis detection methods to estimate the true prevalence. METHODS: We examined 273,126 hospitalizations from 2008 to 2012 at a tertiary-care center to develop surveillance-aimed sepsis detection criteria, based on the presence of the sepsis-explicit International Classification of Diseases, Ninth Revision, Clinical Modification codes (995.92 or 785.52), blood culture orders, and antibiotics administration. We used Bayesian multinomial latent class models to estimate the true prevalence of sepsis, while adjusting for the imperfect sensitivity and specificity and the conditional dependence among the individual criteria. RESULTS: The apparent annual prevalence of sepsis hospitalizations based on explicit International Classification of Diseases, Ninth Revision, Clinical Modification codes were 1.5%, 1.4%, 1.6%, 2.2%, and 2.5% for the years 2008 to 2012. Bayesian posterior estimates for the true prevalence of sepsis suggested that it remained stable from 2008, 19.2% (95% credible interval [CI]: 17.9%, 22.9%), to 2012, 17.8% (95% CI: 16.8%, 20.2%). The sensitivity of sepsis-explicit codes, however, increased from 7.6% (95% CI: 6.4%, 8.4%) in 2008 to 13.8% (95% CI: 12.2%, 14.9%) in 2012. CONCLUSIONS: The true prevalence of sepsis remained high, but stable despite an increase in the sensitivity of sepsis-explicit codes in administrative data.

Photomediated crosslinking of C6-cinnamate derivatized type I collagen.

Synthesis and characterization of cinnamated Type I collagen and its related mechanical properties after photomediated crosslinking were investigated in detail. Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety. The cinnamated collagen was fully characterized by 1H NMR, UV-vis, and circular dichroism (CD) spectroscopy, as well as by rheological and mechanical analyses. Cinnamated collagens with varying degrees of derivatization retained collagen triple helical structure. The rheological spectra of collagen solutions demonstrate that the storage modulus decreases with increasing cinnamate content, owing to a decrease in physical crosslinking. The kinetics of the crosslinking process in both hydrated gels and dry films were monitored by UV-vis spectroscopy and confirmed that crosslinking was complete within 60 min of irradiation. The uniaxial stress-strain behavior of crosslinked collagen films, including Young's modulus and ultimate tensile strength, was comparable to values reported for glutaraldehyde-crosslinked monomeric collagen films. These data demonstrate that derivatization of collagen with photosensitive cinnamate moieties provides a facile route for solid-state crosslinking, thereby improving the mechanical properties of collagen and enhancing the potential applicability of collagen-based materials in tissue engineering and drug delivery.

Viscoelastic and mechanical behavior of recombinant protein elastomers.

Recombinant DNA synthesis was employed to produce elastin-mimetic protein triblock copolymers containing chemically distinct midblocks. These materials displayed a broad range of mechanical and viscoelastic responses ranging from plastic to elastic when examined as hydrated gels and films. These properties could be related in a predictable fashion to polymer block size and structure. While these materials could be easily processed into films and gels, electrospinning proved a feasible strategy for creating protein fibers. All told, the range of properties exhibited by this new class of protein triblock copolymer in combination with their easy processability suggests potential utility in a variety of soft prosthetic and tissue engineering applications.

Prevalence and predictors of compliance with discontinuation of airborne isolation in patients with suspected pulmonary tuberculosis.

OBJECTIVE: Examine the use of airborne isolation by identifying reasons for nontimely discontinuation and predictors of compliance with Centers for Disease Control and Prevention (CDC) guidelines. Compliance with guidelines should result in timely (within 48 hours) discontinuation of isolation in patients without infectious pulmonary tuberculosis (TB). DESIGN: Retrospective, observational study. SETTING: A private, university-affiliated, tertiary-care medical center. PATIENTS: All patients in airborne isolation for suspected pulmonary TB from June through December 2011. METHOD: Chart reviews were performed to identify airborne isolation practices and delayed (greater than 48 hours) or very delayed (greater than 72 hours) discontinuation. We used descriptive statistics and logistic regression to determine independent predictors of nontimely discontinuation of isolation. RESULTS: We identified 113 patients (mean age ± standard deviation, [Formula: see text] years; male sex, 75.2%; white race, 15.9%; mean collection interval ± standard deviation, [Formula: see text] hours). Delayed and very delayed isolation discontinuation was noted in 81% and 49% of patients, respectively. No significant differences in demographic characteristics and clinical characteristics were identified between groups. Predictors of timely (within 48 hours) airborne isolation discontinuation included use of alternate diagnosis for discontinuation of isolation ([Formula: see text]), early infectious diseases (ID) consultation ([Formula: see text]), pulmonary consultation ([Formula: see text]), average sputum collection interval less than 24 hours ([Formula: see text]), and need for more than 1 induced sputum specimen ([Formula: see text]). Adjusting for potential confounders, pulmonary consultation (odds ratio [OR] [95% confidence interval (CI)], 0.14 [0.03-0.58]), alternate diagnosis for discontinuation of isolation (OR [95% CI], 4.5 [1.3-15.8]), and early ID consultation (OR [95% CI], 4.0 [1.1-14.8]) were independently associated with timely discontinuation. CONCLUSIONS: Timely airborne isolation discontinuation occurs in only 18.6% of cases and is an opportunity for cost savings, improved efficiency, and potentially patient safety and satisfaction.

Photo-cross-linking of type I collagen gels in the presence of smooth muscle cells: mechanical properties, cell viability, and function.

The effectiveness of photomediated cross-linking of type I collagen gels in the presence of rat aortic smooth muscle cells (RASMC) as a method to enhance gel mechanical properties while retaining native collagen triple helical structure and maintaining high cell viability was investigated. Collagen was chemically modified to incorporate an acrylate moiety. Collagen methacrylamide was cast into gels in the presence of a photoinitiator along with RASMC. The gels were cross-linked using visible light irradiation. Neither acrylate modification nor the cross-linking reaction altered collagen triple helical content. The cross-linking reaction, however, moved the denaturation temperature beyond the physiologic range. A twelve-fold increase in shear modulus was observed after cross-linking. Cell viability in the range of 70% (n = 4, p > 0.05) was observed in the photo-cross-linked gels. Moreover the cells were able to contract the cross-linked gel in a manner commensurate with that observed for natural type I collagen. Methacrylate-mediated photo-cross-linking is a facile route to improve mechanical properties of collagen gels in the presence of cells while maintaining high cell viability. This enhances the potential for type I collagen gels to be used as scaffolds for tissue engineering.