Medication contaminants as a potential cause of anaphylaxis to vincristine.

Vincristine (VCR) is a vinca alkaloid and common chemotherapeutic that is used to treat multiple pediatric and adult malignancies. Despite its common use, cases of anaphylaxis to VCR are rare and typically isolated to a single individual. We report a series of eight patients with adverse reactions to VCR over the course of 11 months at a single institution, four of which progressed to anaphylaxis and one of which resulted in cardiac arrest. Mass spectrometry analysis of medication lots was performed to test for possible contaminant(s). Our findings highlight the risk of anaphylaxis during therapy with VCR.

Litter quality versus soil microbial community controls over decomposition: a quantitative analysis.

The possible effects of soil microbial community structure on organic matter decomposition rates have been widely acknowledged, but are poorly understood. Understanding these relationships is complicated by the fact that microbial community structure and function are likely to both affect and be affected by organic matter quality and chemistry, thus it is difficult to draw mechanistic conclusions from field studies. We conducted a reciprocal soil inoculum × litter transplant laboratory incubation experiment using samples collected from a set of sites that have similar climate and plant species composition but vary significantly in bacterial community structure and litter quality. The results showed that litter quality explained the majority of variation in decomposition rates under controlled laboratory conditions: over the course of the 162-day incubation, litter quality explained nearly two-thirds (64%) of variation in decomposition rates, and a smaller proportion (25%) was explained by variation in the inoculum type. In addition, the relative importance of inoculum type on soil respiration increased over the course of the experiment, and was significantly higher in microcosms with lower litter quality relative to those with higher quality litter. We also used molecular phylogenetics to examine the relationships between bacterial community composition and soil respiration in samples through time. Pyrosequencing revealed that bacterial community composition explained 32 % of the variation in respiration rates. However, equal portions (i.e., 16%) of the variation in bacterial community composition were explained by inoculum type and litter quality, reflecting the importance of both the meta-community and the environment in bacterial assembly. Taken together, these results indicate that the effects of changing microbial community composition on decomposition are likely to be smaller than the potential effects of climate change and/or litter quality changes in response to increasing atmospheric CO2 concentrations or atmospheric nutrient deposition.

Bacteria and diatom co-occurrence patterns in microbial mats from polar desert streams.

The ephemeral stream habitats of the McMurdo Dry Valleys of Antarctica support desiccation and freeze-tolerant microbial mats that are hot spots of primary productivity in an otherwise inhospitable environment. The ecological processes that structure bacterial communities in this harsh environment are not known; however, insights from diatom community ecology may prove to be informative. We examined the relationships between diatoms and bacteria at the community and taxon levels. The diversity and community structure of stream microbial mats were characterized using high-throughput pyrosequencing for bacteria and morphological identification for diatoms. We found significant relationships between diatom communities and the communities of cyanobacteria and heterotrophic bacteria, and co-occurrence analysis identified numerous correlations between the relative abundances of individual diatom and bacterial taxa, which may result from species interactions. Additionally, the strength of correlations between heterotrophic bacteria and diatoms varied along a hydrologic gradient, indicating that flow regime may influence the overall community structure. Phylogenetic consistency in the co-occurrence patterns suggests that the associations are ecologically relevant. Despite these community- and taxon-level relationships, diatom and bacterial alpha diversity were inversely correlated, which may highlight a fundamental difference between the processes that influence bacterial and diatom community assembly in these streams. Our results therefore demonstrate that the relationships between diatoms and bacteria are complex and may result from species interactions as well as niche-specific processes.

Conversion from prolonged intravenous fentanyl infusion to enteral methadone in critically ill children.

AIM: To describe our institutional experience with conversion from intravenous (IV) fentanyl infusion directly to enteral methadone and occurrence of withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation and analgesia. METHODS: With Institutional Review Board approval, we retrospectively studied consecutively admitted invasively mechanically ventilated children (0-18 years) sedated with IV fentanyl infusion > 5 d and subsequently converted directly to enteral methadone. Data were obtained on subject demographics, illness severity, daily IV fentanyl and enteral methadone dosing, time to complete conversion, withdrawal scores (WAT-1), pain scores, and need for rescue opioids. Patients were classified as rapid conversion group (RCG) if completely converted ≤ 48 h and slow conversion group (SCG) if completely converted in > 48 h. Primary outcome was difference in WAT-1 scores at 7 d. Secondary outcomes included differences in overall pain scores, and differences in daily rescue opioids. RESULTS: Compared to SCG (n = 21), RCG (n = 21) had lower median WAT-1 scores at 7 d (2.5 vs 5, P = 0.027). Additionally, RCG had lower overall median pain scores (3 vs 6, P = 0.007), and required less median daily rescue opioids (3 vs 12, P = 0.003) than SCG. The starting daily median methadone dose was 2.3 times the daily median fentanyl dose in the RCG, compared to 1.1 times in the SCG (P = 0.049). CONCLUSION: We observed wide variation in conversion from IV fentanyl infusion directly to enteral methadone and variability in withdrawal in critically ill mechanically ventilated children exposed to prolonged sedation. In those children who converted successfully from IV fentanyl infusion to enteral methadone within a period of 48 h, a methadone:fentanyl dose conversion ratio of approximately 2.5:1 was associated with less withdrawal and reduced need for rescue opioids.

Safety of Automatic End Dates for Antimicrobial Orders to Facilitate Stewardship.

Following implementation of automatic end dates for antimicrobial orders to facilitate antimicrobial stewardship at a large, academic children's hospital, no differences were observed in patient mortality, length of stay, or readmission rates, even among patients with documented bacteremia. Infect Control Hosp Epidemiol 2016;37:974-978.

Patterns and processes of microbial community assembly.

Recent research has expanded our understanding of microbial community assembly. However, the field of community ecology is inaccessible to many microbial ecologists because of inconsistent and often confusing terminology as well as unnecessarily polarizing debates. Thus, we review recent literature on microbial community assembly, using the framework of Vellend (Q. Rev. Biol. 85:183-206, 2010) in an effort to synthesize and unify these contributions. We begin by discussing patterns in microbial biogeography and then describe four basic processes (diversification, dispersal, selection, and drift) that contribute to community assembly. We also discuss different combinations of these processes and where and when they may be most important for shaping microbial communities. The spatial and temporal scales of microbial community assembly are also discussed in relation to assembly processes. Throughout this review paper, we highlight differences between microbes and macroorganisms and generate hypotheses describing how these differences may be important for community assembly. We end by discussing the implications of microbial assembly processes for ecosystem function and biodiversity.

Changes in assembly processes in soil bacterial communities following a wildfire disturbance.

Although recent work has shown that both deterministic and stochastic processes are important in structuring microbial communities, the factors that affect the relative contributions of niche and neutral processes are poorly understood. The macrobiological literature indicates that ecological disturbances can influence assembly processes. Thus, we sampled bacterial communities at 4 and 16 weeks following a wildfire and used null deviation analysis to examine the role that time since disturbance has in community assembly. Fire dramatically altered bacterial community structure and diversity as well as soil chemistry for both time-points. Community structure shifted between 4 and 16 weeks for both burned and unburned communities. Community assembly in burned sites 4 weeks after fire was significantly more stochastic than in unburned sites. After 16 weeks, however, burned communities were significantly less stochastic than unburned communities. Thus, we propose a three-phase model featuring shifts in the relative importance of niche and neutral processes as a function of time since disturbance. Because neutral processes are characterized by a decoupling between environmental parameters and community structure, we hypothesize that a better understanding of community assembly may be important in determining where and when detailed studies of community composition are valuable for predicting ecosystem function.

CEL-2000: A therapeutic vaccine for rheumatoid arthritis arrests disease development and alters serum cytokine/chemokine patterns in the bovine collagen type II induced arthritis in the DBA mouse model.

The mouse model of collagen induced arthritis (CIA) effectively mimics human disease and thus is useful for testing and development of rheumatoid arthritis (RA) therapies. We developed a Ligand Epitope Antigen Presentation System (LEAPS) peptide hetero-conjugate vaccine containing an epitope of human collagen type II (CEL-2000) that acted as a therapeutic vaccine in the collagen induced arthritis (CIA) mouse model. LEAPS technology converts a small peptide containing a disease specific epitope into an immunogen by attaching it to an immune or T cell binding peptide (I/TCBL). For CEL-2000, a peptide from human collagen type II (254-273) is attached to the I/TCBL peptide from human beta2 microglobulin (J). Treatment with CEL-2000 limited disease (CIA) progression, as demonstrated by reduced Arthritic Index (AI) score, and footpad swelling. Efficacy was confirmed by histopathological microscopic examination of tissues at the end of the study. CEL-2000 limited disease progression as well or better than the etanercept (Enbrel) therapeutic control with significantly better histopathological results than the etanercept treated mice. Most interestingly, CEL-2000 therapy modulated serum cytokine levels with an increase in IL-12p70 and IL-10, which are not seen with etanercept therapy, and reduced IL-17 and TNF-alpha, also seen with etanercept, among other cytokines studied. CEL-2000 was safe and well tolerated for the mice that received 5 injections given every 2weeks in a 90day study supporting its potential usage for long term therapy. These studies demonstrate that fewer treatments with CEL-2000 provide therapy at least as effective as etanercept by specifically modulating the disease producing autoimmune response.