Rapid and Robust Identification of Sepsis Using SeptiCyte RAPID in a Heterogeneous Patient Population

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis

THE TREATMENT OF COCCIDIOIDOMYCOSIS

SUMMARYTherapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection

Rapid and robust identification of sepsis using SeptiCyte RAPID in a heterogeneous patient population

Background/Objective: SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194]. In this study, we present the results from a detailed stratification analysis in which SeptiCyte RAPID performance was evaluated in the same cohort across patient groups and subgroups encompassing different demographics, comorbidities and disease, sources and types of pathogens, interventional treatments, and clinically defined phenotypes. The aims were to identify variables that might affect the ability of SeptiCyte RAPID to discriminate between sepsis and SIRS and to determine if any patient subgroups appeared to present a diagnostic challenge for the test. Methods: (1) Subgroup analysis, with subgroups defined by individual demographic or clinical variables, using conventional statistical comparison tests. (2) Principal component analysis and k-means clustering analysis to investigate phenotypic subgroups defined by unique combinations of demographic and clinical variables. Results: No significant differences in SeptiCyte RAPID performance were observed between most groups and subgroups. One notable exception involved an enhanced SeptiCyte RAPID performance for a phenotypic subgroup defined by a combination of clinical variables suggesting a septic shock response. Conclusions: We conclude that for this patient cohort, SeptiCyte RAPID performance was largely unaffected by key variables associated with heterogeneity in patients suspected of sepsis.peer-reviewe

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.peer-reviewe

Increased risk of 100-day and 1-year infection-related mortality and complications in haploidentical stem cell transplantation

Jeremy Chang,1 Mindy Hsiao,2 Emily Blodget,3 Mojtaba Akhtari21Department of Internal Medicine, Los Angeles County and University of Southern California, Los Angeles, CA, USA; 2Department of Hematology/Oncology, Norris Comprehensive Cancer Center, Los Angeles, CA, USA; 3Division of Infectious Diseases, University of Southern California, Los Angeles, USABackground: While haploidentical transplantation has led to the near-universal availability of donors, several challenges for this form of transplant still exist. This study sought to investigate the rates of infection-related mortality and other complications following haploidentical vs nonhaploidentical transplant.Methods: We conducted a retrospective cohort study in adults with various malignant and benign hematological conditions who underwent allogeneic hematopoietic stem cell transplantation from 2011 to 2018. One hundred-day and 1-year overall survival were defined as survival from the time of transplant until 100 days or 1 year later.Results: A total of 187 patients were included in this study, with 45 (24.1%) receiving transplants from haploidentical donors and 142 (75.9%) from nonhaploidentical donors. There were similar rates of acute graft-versus-host disease (GVHD) (40% vs 38% in haploidentical vs nonhaploidentical recipients, P=0.86) and chronic GVHD (44.4% vs 43.7%, P=1). Rates of 100-day and 1-year infection-related mortality were significantly higher in the haploidentical group compared to the nonhaploidentical group (8.9% vs 1.4% at 100 days, P=0.03, and 15.9% vs 3.8% at 1 year, P=0.01). There were also higher rates of cytomegalovirus infections (59.1% vs 23.8%, P<0.01), BK virus-associated hemorrhagic cystitis (40.9% vs 8.4%, P<0.01), and BK viremia (15.9% vs 0.8%, P<0.01) in haploidentical recipients.Conclusions: Despite the use of identical antimicrobial prophylactic and treatment agents, haploidentical recipients were found to have significantly increased rates of 100-day and 1-year infection-related mortality as well as several other infectious complications.Keywords: infection, survival, haploidentical stem cell transplantatio

A self-reconfiguring platform

Abstract. A self-reconfiguring platform is reported that enables an FPGA to dynamically reconfigure itself under the control of an embedded microprocessor. This platform has been implemented on Xilinx Virtex II¦¨ § and Virtex II Pro¦© § devices. The platform’s hardware architecture has been designed to be the low level configuration interface. The Xilinx Partial Reconfiguration Toolkit (XPART), the higher level of the two APIs, provides methods for reading and modifying select FPGA resources. It also provides support for relocatable partial bitstreams. The presented self-reconfiguring platform enables embedded applications to take advantage of dynamic partial reconfiguration without requiring external circuitry.