Posttranscriptional Regulation in Response to Different Environmental Stresses in Campylobacter jejuni.

The survival strategies that Campylobacter jejuni (C. jejuni) employ throughout its transmission and infection life cycles remain largely elusive. Specifically, there is a lack of understanding about the posttranscriptional regulation of stress adaptations resulting from small noncoding RNAs (sRNAs). Published C. jejuni sRNAs have been discovered in specific conditions but with limited insights into their biological activities. Many more sRNAs are yet to be discovered as they may be condition-dependent. Here, we have generated transcriptomic data from 21 host- and transmission-relevant conditions. The data uncovered transcription start sites, expression patterns and posttranscriptional regulation during various stress conditions. This data set helped predict a list of putative sRNAs. We further explored the sRNAs' biological functions by integrating differential gene expression analysis, coexpression analysis, and genome-wide sRNA target prediction. The results showed that the C. jejuni gene expression was influenced primarily by nutrient deprivation and food storage conditions. Further exploration revealed a putative sRNA (CjSA21) that targeted tlp1 to 4 under food processing conditions. tlp1 to 4 are transcripts that encode methyl-accepting chemotaxis proteins (MCPs), which are responsible for chemosensing. These results suggested CjSA21 inhibits chemotaxis and promotes survival under food processing conditions. This study presents the broader research community with a comprehensive data set and highlights a novel sRNA as a potential chemotaxis inhibitor. IMPORTANCE The foodborne pathogen C. jejuni is a significant challenge for the global health care system. It is crucial to investigate C. jejuni posttranscriptional regulation by small RNAs (sRNAs) in order to understand how it adapts to different stress conditions. However, limited data are available for investigating sRNA activity under stress. In this study, we generate gene expression data of C. jejuni under 21 stress conditions. Our data analysis indicates that one of the novel sRNAs mediates the adaptation to food processing conditions. Results from our work shed light on the posttranscriptional regulation of C. jejuni and identify an sRNA associated with food safety.

Outcomes with enoxaparin dose reductions during thrombocytopenia in patients with hematopoietic stem cell transplantation (HSCT).

INTRODUCTION: Appropriate dosing of therapeutic anticoagulation during periods of thrombocytopenia remains uncertain for patients undergoing hematopoietic stem cell transplants (HSCT). There is a paucity of literature on treatment outcomes for HSCT patients treated with non-prophylactic, but reduced doses of therapeutic anticoagulation during thrombocytopenia. The primary objective was to determine the incidence of major bleeding events during thrombocytopenia when reduced-dose enoxaparin was administered. METHODS: This is a retrospective review of patients with a venous thromboembolic event (VTE) who underwent HSCT and received reduced-dose enoxaparin during thrombocytopenia at the Massachusetts General Hospital (MGH) from April 1, 2016 to August 31, 2018. Incidence of recurrent VTE and bleeding events for up to one month were investigated. Rates of recurrent VTE and enoxaparin dose adjustments (0.5 mg/kg twice daily vs 1 mg/kg daily) were also reviewed. RESULTS: Out of 172 patients reviewed, 27 patients met inclusion criteria. There were no recurrent VTEs within one month of initial enoxaparin dose reduction. There was one major bleeding episode that occurred while a patient was on full-dose enoxaparin; believed to be related to cyclophosphamide cardiopulmonary toxicity and resulted in death. There were six non-major bleeding episodes, only one of which was clinically significant and resulted in the discontinuation of enoxaparin. CONCLUSION: Our evaluation of therapeutic enoxaparin dose reductions for thrombocytopenia in the HSCT patient population found this practice to be effective in reducing the recurrence of VTE with no major bleeding adverse events. However, the rate of non-significant minor bleeds should be monitored while on reduced-dose enoxaparin.

Incidence of Invasive Fungal Infections in Acute Myeloid Leukemia Without Antifungal Prophylaxis.

BACKGROUND: Antifungal prophylaxis during induction for acute myeloid leukemia (AML) varies according to local rates of invasive fungal infections (IFIs). We evaluated fluconazole prophylaxis and no antifungal prophylaxis, as a natural interrupted time-series study to assess survival and infection complications. PATIENTS AND METHODS: We identified patients with AML ≥ 18 years old undergoing induction chemotherapy during 2 time periods: period 1, fluconazole prophylaxis from August 1, 2013 to September 30, 2015, and period 2, no prophylaxis from October 1, 2015 to December 31, 2017. The primary outcome was incidence of proven or probable IFI. Secondary outcomes included types of IFIs and 60-day overall survival (OS). IFI was defined by the 2002 European Organization for Research and Treatment of Cancer/Mycoses Study Group Consensus criteria. RESULTS: One hundred forty-four patients received induction chemotherapy over the 2 time periods. In the prophylaxis versus no-prophylaxis groups, the rate of proven or probable IFIs was 4 (5%) of 87 versus 12 (21%) of 57 (P = .01). The total number of proven IFIs was 3 (3%) of 87 versus 4 (7%) of 57 (P = .44), whereas probable IFIs were 1 (1%) of 87 versus 8 (14%) of 57 (P < .01). No difference was observed in fungemia. Incidence of IFIs was too low to detect resistance patterns. OS at 60 days was improved in with fluconazole prophylaxis compared with no prophylaxis (hazard ratio, 0.329; 95% confidence interval, 0.12-0.89; P = .028). CONCLUSION: Observed rates of proven or probable IFI were lower in the fluconazole prophylaxis group versus the no-prophylaxis group. Sixty-day OS was higher with fluconazole prophylaxis. Further study is required to evaluate how fluconazole may impart the differences in survival seen in this analysis.