The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for liver allograft function is unclear. Our previous studies have shown that humoral alloreactivity frequently accompanies acute cellular rejection (ACR). In the present study, we set out to determine whether pretransplant HLA-DSAs correlate with clinically significant ACR in the first 90 days after transplantation and, if so, to determine their predictive values. Class I HLA-DSAs and class II HLA-DSAs were determined by single-antigen bead flow cytometry for 113 consecutive adult transplants. A statistical analysis was performed for data from 109 consecutive patients with graft survival greater than or equal to 90 days. All patients who developed biochemical graft dysfunction underwent liver biopsy for hematoxylin-eosin and complement component 4d staining. Cox proportional hazards models and associated hazard ratios revealed a significant association of pretransplant HLA-DSAs with clinically significant ACR: this association started with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard ratio 5 2.7, P < 0.01) and class II (hazard ratio 5 6.0, P < 0.01). Pretransplant HLA-DSAs were associated with an increased risk of ACR: P < 0.01 for class I (42% versus 18%), P < 0.001 for class II (37% versus 7%), and P < 0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an MFI 1000 had the best positive predictive value for clinically significant ACR at 46%, whereas class I or II HLA-DSAs with an MFI 300 had the best negative predictive value at 97.1%. Although our study was based on consecutive patients, it was limited by the relatively low number of single-center subjects. In conclusion, the present study indicates that pretransplant HLA-DSAs, even at low levels of allosensitization, correlate with the risk of clinically significant ACR. Our findings suggest that anti-human leukocyte antigen antibodies could serve as donor-specific markers of immunoreactivity to the liver graft.
In a patient population predisposed to BPAR, discharge tacrolimus trough concentration less than 8 ng/mL was associated with a nearly two times greater risk of BPAR.
It is essential to provide optimal pharmacotherapy for each organ donor to ensure organ recovery and donation. Typical medications used in organ donors include agents for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions.
The gap between supply and demand for available organs has resulted in numerous deaths of patients on the transplant waiting list each year. Given the substantial public health impact of the organ shortage crisis, efforts have been focused on the use of educational interventions aimed both at the public and health care professionals to spread awareness of the disparity in organ supply and demand and ultimately improve organ donation rates. Transplant pharmacists are fundamental members of transplant multidisciplinary teams and are expected to promote organ and tissue awareness in an effort to decrease the morbidity and mortality of patients on the transplant waiting list. The role of pharmacists and pharmacy students in the promotion of organ donation awareness is expanding.
The abundance of Aulacoseira granulata (Ehrenburg) Simonsen and Gloeocystis planctonica (West & G.S.West) Lemmermann was assessed during the summers of 2005 and 2010 in the eutrophic Fox River, Wisconsin, USA. In both years, a mid-summer bloom of G. planctonica was followed by the rapid growth of A. granulata. Laboratory experiments in which A. granulata was grown in cell-free filtrate of a G. planctonica culture revealed that the growth of A. granulata was stimulated in the G. planctonica-treated medium relative to controls. This effect was detected when dormant A. granulata cells were used as the source culture for the experiment but not when actively growing cells were used. Dormant A. granulata also grew more rapidly in river water collected after the 2010 G. planctonica bloom relative to river water collected before the bloom. These results suggest that the summer bloom of A. granulata in the river was stimulated by G. planctonica. This relationship can be described as stimulated rejuvenation, an interaction where the transition of an algal resting stage into active growth is triggered by exposure to another species.
BackgroundSolid organ transplant (SOT) patients are at high risk for Clostridium difficile infections (CDI) due to chronic immunosuppression and a propensity to receive antimicrobials. Management of CDI in SOT patients poses unique challenges as this population has disease-altered clinical and laboratory parameters. The objective of this study was to assess concordance between various CDI severity scales and the Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) guidelines.MethodsThis retrospective study included all SOT recipients with a first CDI episode following transplant and time-matched (2:1) to non-SOT patients experiencing first CDI episodes between 2008 and 2016. The primary endpoint was concordance rates of CDI episodes considered mild-moderate or severe/severe-complicated in published CDI scales compared with the SHEA/IDSA guidelines. We also sought to compare the distribution of CDI severity across all scales between SOT and non-SOT patients.ResultsOverall, 32 SOT patients and 64 non-SOT patients were included. The SOT group had significantly higher leukopenia rates at CDI diagnosis; however, the magnitude of serum creatinine change did not differ between groups. According to the SHEA/IDSA scale, CDI episodes in SOT recipients were categorized as mild-moderate and severe/severe-complicated in 23 (72%) and 9 (28%) patients, respectively. Overall concordance rates among SHEA/IDSA guidelines and other scales ranged from 28% to 72%. Concordance rates were highest for mild-moderate CDI with Belmares and for severe/severe-complicated CDI with ESCMID (Table 1). No scale evenly categorized SOT and non-SOT patients across all severities (Figure 1).ConclusionSeverity scales with heavy emphasis on white blood cell counts may not adequately categorize SOT patients. Immunocompromised status may need to be considered on its own when categorizing CDI severity and prescribing therapy.Table 1
Number (%) of Severity Classification-Concordant CDI Episodes,
in Comparison to SHEA/IDSA Guidelines
Overall
n = 32
Mild/Moderate
n = 23
Severe or Severe-Complicated
n = 9
AST
23 (71.9)18 (78.3)5 (55.6)
ESCMID
9 (28.1)09 (100)
Zar
20 (62.5)13 (56.5)7 (77.8)
Belmares
22 (68.8)22 (95.7)0Disclosures
C. D. Alonso, Merck: Grant Investigator and Scientific Advisor, Research grant sanofi pasteur: Investigator and Scientific Advisor, Research support GSK: Investigator, Research support; E. B. Hirsch, Merck: Grant Investigator, Grant recipient The Medicines Company: Speaker’s Bureau, Speaker honorarium
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