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Open Access Publications from the University of California

Scholarly Works (44 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2022)
    Cover page: Editorial: Immune Aging: Implications for TransplantationCreative Commons 'BY-NC-ND' version 4.0 license
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2014)

    Background: Quilty effect (QE), an infiltrate consisting of small vessels, B-cells, and T-cells is found exclusively in endomyocardial biopsies from heart transplant recipients. We hypothesize that mechanical circulatory support devices (MCSD) used as a bridge to transplantation (BTT) predispose orthotropic heart transplant (OHT) recipients to developing QE. We sought to 1) define the predictors of QE in those BTT with MCSD, and 2) determine the impact of QE on post-OHT outcomes.

    Methods: A retrospective chart review was performed of all adult patients with MCSD, implanted for BTT, and successfully transplanted between 1996 and 2012 (N = 115). Using logistic regression, time-to-event curves, and Cox Proportional Hazards, clinical parameters were evaluated as predictors of the primary outcome, QE, and secondary outcomes of acute cellular rejection (ACR), pathologic antibody mediated rejection (pAMR), and death.

    Results: 100 subjects developed QE (86.9%); 49 (43%) developed QE within the first 15 days post-OHT (early QE). Cyclosporine (CsA) use was protective of early QE (adjusted OR 0.29, p=0.02). Donor age decreased odds of ever developing QE (adjusted OR 0.94, p=0.03). QE increased one's odds of developing biopsy-proven ACR (adjusted OR 13.2, p=0.02). Cox Regression model revealed an adjusted HR of 0.61 (p=0.0007) for every 10-years of donor age.

    Conclusions: QE incidence in this population was higher than prior studies have found. CsA use and donor age were associated with QE development, consistent with previously published reports. Studies comparing a BTT population with those who proceed directly to OHT, and assessing the recurrent nature of QE are necessary to better understand QE in this cohort.

      Cover page: Predictors of Quilty Effect in a Population Bridged to Orthotropic Heart Transplantation with a Mechanical Circulatory Support Device
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2022)
      Prior research has identified frailty, comorbidity, and age as predictors of outcomes for patients with coronavirus disease 2019 (COVID-19), including mortality. However, it remains unclear how these factors play different roles in COVID-19 prognosis. This study focused on correlations between frailty, comorbidity and age, and their correlations to discharge outcome and length-of-stay in hospitalized patients with COVID-19. Clinical data was collected from 56 patients who were ≥50 years old and admitted from March 2020 to June 2020 primarily for COVID-19. Frailty Risk Score (FRS) and the Charlson Comorbidity Index (CCI) were used for assessment of frailty and comorbidity burden, respectively. Age had significant positive correlation with FRS and CCI (P < .001, P < .001, respectively). There was also significant positive correlation between FRS and CCI (P < .001). For mortality, patients who died during their hospitalization had significantly higher FRS and CCI (P = .01 and P < .001, respectively) but were not significantly older than patients who did not. FRS, CCI, and age were all significantly associated when looking at overall adverse discharge outcome (transfer to other facility or death) (P < .001, P = .005, and P = .009, respectively). However, none of the 3 variables were significantly correlated with length-of-stay. Multivariate analysis showed FRS (P = .007) but not patient age (P = .967) was significantly associated with death. We find that frailty is associated with adverse outcomes from COVID-19 and supplants age in multivariable analysis. Frailty should be part of risk assessment of older adults with COVID-19.
        Cover page: Predictors of COVID-19 outcomes: Interplay of frailty, comorbidity, and age in COVID-19 prognosis.
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2020)
        We report here a fatal case of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a renal transplant patient without a travel history in the prior year, from whom 2 genetically different CRKP (sequence type 14 [ST14] and ST2497) strains carrying the same plasmids and antimicrobial resistance genes, including blaNDM-1, blaOXA-232, blaCTX-M-15, armA, and tet(D), were isolated from blood and the abdominal cavity. The isolates were susceptible to colistin, tigecycline, eravacycline, and cefiderocol, which was used to treat the CRKP in combination with ceftazidime-avibactam and polymyxin B and resulted in bacterial clearance. Despite the aggressive treatment, the patient died of ischemic colitis and multiorgan failure.
          Cover page: Coinfections of Two Strains of NDM-1- and OXA-232-Coproducing Klebsiella pneumoniae in a Kidney Transplant Patient.
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2023)
          We describe a case of New Delhi metallo-β-lactamase 1-producing carbapenem-resistant Pseudomonas aeruginosa (CRPA) in a transplant patient with multiple hospitalizations in California, USA. Whole-genome sequencing revealed the isolate was genetically distinctive, despite ≈95% similarity to other global strains. The patient's lack of international travel suggests this CRPA was acquired domestically.
            Cover page: Domestically Acquired NDM-1–Producing Pseudomonas aeruginosa, Southern California, USA, 2023 - Volume 29, Number 11—November 2023 - Emerging Infectious Diseases journal - CDCCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2022)
            Older kidney transplant recipients demonstrate increased rates of infection, and lower rates of rejection, compared with younger kidney transplant recipients. However, the mechanism behind this observation remains unknown. To develop a multifaceted view of age-associated immune dysfunction, we determined the function and phenotype of T cells predisposing to vulnerability to infection on a molecular level. Overlapping peptide pools representing the dominant CMV antigens were used to stimulate PBMC collected from 51 kidney transplant recipients, using cytokine secretion to determine specificity and intensity of response. Staphylococcal endotoxin B (SEB) was analyzed in parallel. To define immune cell subsets, we used single cell RNA sequencing (scRNAseq) to evaluate cellular surface markers and gene expression. We found increased frequency of SEB- and CMV-specific T cells was associated with freedom from infection, especially in older patients. Spatialized t-SNE analysis revealed decreased frequency of naïve T cells, increased frequency of TEMRA cells, and decreased frequency of IFNγ secreting T cells in patients with infection. Application of scRNAseq analysis revealed increased frequency of terminally differentiated T cells expressing NK-associated receptors and inhibitory markers. These findings offer unique insight into the mechanism behind vulnerability to infection in the kidney transplant recipient, revealing a specific T cell subtype of impaired antigen response and terminal effector phenotype as markers of T cell senescence.
              Cover page: T cell senescence and impaired CMV-specific response are associated with infection risk in kidney transplant recipients
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)

              Introduction

              Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown.

              Methods

              This single-center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart-review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep.

              Results

              We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025).

              Conclusion

              SPPB and chart-review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.
                Cover page: Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2021)

                Background

                Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation.

                Methods

                We reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3-year period at a high-volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis.

                Results

                Despite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100 days after transplantation. For high risk patients, median time to DNAemia was 75 days after transplantation, and the majority of patients had experienced dose-reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64 days (P = .029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group.

                Conclusions

                Guidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation.
                  Cover page: Early cytomegalovirus DNAemia and antiviral dose adjustment in high vs intermediate risk kidney transplant recipients
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2020)
                  We report here a fatal case of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in a renal transplant patient without a travel history in the prior year, from whom 2 genetically different CRKP (sequence type 14 [ST14] and ST2497) strains carrying the same plasmids and antimicrobial resistance genes, including blaNDM-1, blaOXA-232, blaCTX-M-15, armA, and tet(D), were isolated from blood and the abdominal cavity. The isolates were susceptible to colistin, tigecycline, eravacycline, and cefiderocol, which was used to treat the CRKP in combination with ceftazidime-avibactam and polymyxin B and resulted in bacterial clearance. Despite the aggressive treatment, the patient died of ischemic colitis and multiorgan failure.
                    Cover page: Coinfections of Two Strains of NDM-1- and OXA-232-Coproducing Klebsiella pneumoniae in a Kidney Transplant Patient.
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2024)
                    Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D+/R-) patients have greater viremia risk than D-/R-. The majority of patients are R+ having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at loci associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R+ individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R+ patients at high viremia risk.
                      Cover page: An epigenetic human cytomegalovirus infection score predicts viremia risk in seropositive lung transplant recipients.
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