Publications by authors named "Tahli Singer-Englar"

9 Publications

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Long-term outcomes after heart transplantation using ex vivo allograft perfusion in standard risk donors: A single-center experience.

Clin Transplant 2022 Jan 14:e14591. Epub 2022 Jan 14.

Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Introduction: The Organ Care System (OCS) is an ex vivo perfusion platform for donor heart preservation. Short/mid-term post-transplant outcomes after its use are comparable to standard cold storage (CS). We evaluated long-term outcomes following its use.

Methods: Between 2011 and 2013, 38 patients from a single center were randomized as a part of the PROCEED II trial to receive allografts preserved with CS (n = 19) or OCS (n = 19). Endpoints included 8-year survival, survival free from graft-related deaths, freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and rejections.

Results: Eight-year survival was 57.9% in the OCS group and 73.7% in the CS group (p = .24). Freedom from CAV was 89.5% in the OCS group and 67.8% in the CS group (p = .13). Freedom from NF-MACE was 89.5% in the OCS group and 67.5% in the CS group (p = .14). Eight-year survival free from graft-related death was equivalent between the two groups (84.2% vs. 84.2%, p = .93). No differences in rejection episodes were observed (all p > .5).

Conclusions: In select patients receiving OCS preserved allografts, late post-transplant survival trended lower than those transplanted with an allograft preserved with CS. This is based on a small single-center series, and larger numbers are needed to confirm these findings.
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http://dx.doi.org/10.1111/ctr.14591DOI Listing
January 2022

Advanced heart failure and heart transplantation in adult congenital heart disease in the current era.

Clin Transplant 2021 Nov 12;35(11):e14451. Epub 2021 Sep 12.

Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Background: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center.

Methods: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery.

Results: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21).

Conclusion: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.
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http://dx.doi.org/10.1111/ctr.14451DOI Listing
November 2021

Mechanical Circulatory Support as a Bridge-to-Transplant Candidacy: When Does It Work?

ASAIO J 2021 Jun 1. Epub 2021 Jun 1.

From the Departments of Cardiology and Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai, Los Angeles, California.

Durable mechanical circulatory support (dMCS) devices can be offered as a bridge-to-transplant (BTT) or as a bridge-to-candidacy (BTC) strategy for candidates with contraindications to transplant listing, including pulmonary hypertension (BTC-PH), morbid obesity (BTC-Obes), social issues (BTC-Soc), or chronic illness (BTC-Illness). An understanding of the trajectory of BTC patients could guide future triage of advanced heart failure patients who are not candidates for transplantation. We performed a retrospective review all patients who underwent dMCS implantation as either BTT (206 patients) or BTC (114 patients) at our center from January 1, 2010, to March 31, 2020. There was no significant difference in mortality between BTC patients and BTT patients. Compared with the BTT group, significantly more patients in the BTC-PH group were transplanted (81% vs. 63%; p < 0.05) and significantly fewer patients in the BTC-Obes group (44%; p < 0.05) and BTC-Soc group (39%; p < 0.05) were transplanted. Additionally, the readmission rate was higher for those in the BTC-Obes (6.2 vs. 2.1; p < 0.05) and BTC-Soc (3.9 vs. 2.1; p < 0.05) groups. Bridge-to-candidacy patients generally had poorer post-dMCS trajectories than BTT patients. Centers should not be dissuaded from pursuing a BTC strategy for qualified patients; however, careful consideration of potential adverse outcomes is necessary.
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http://dx.doi.org/10.1097/MAT.0000000000001500DOI Listing
June 2021

Heart transplant in Jehovah's Witness patients: A case-control study.

J Heart Lung Transplant 2021 07 21;40(7):575-579. Epub 2021 Mar 21.

Cedars-Sinai Medical Center, the Department of Cardiology, Smidt Heart Institute, Cedars-Sinai, Los Angeles, California. Electronic address:

Heart transplantation (HTx) improves quality of life and survival in patients with advanced heart failure. Jehovah's Witnesses (JW) patients decline blood transfusion (including red cells, plasma and platelets) and are prohibited from heart transplantation at many centers. We report our experience with 20 consecutive JW patients with advanced heart failure who declined blood products referred to our center for HTx consideration. Of these, 7 were declined for transplant due to prior sternotomy, need for multi-organ transplant, or being too well. Of 13 JW patients accepted for heart transplant listing, 8 underwent HTx at our center. Compared to non-JW controls without prior cardiac surgery matched for age and listing status, JW HTx recipients had comparable incidence of primary graft dysfunction, rejection, allograft vasculopathy, and survival and hemoglobin up to 1 year. With appropriate selection, patients who are JW and decline blood products may successfully undergo heart transplantation.
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http://dx.doi.org/10.1016/j.healun.2021.03.014DOI Listing
July 2021

The impact of depression on heart transplant outcomes: A retrospective single-center cohort study.

Clin Transplant 2021 03 5;35(3):e14204. Epub 2021 Jan 5.

Department of Cardiology, Cedars-Sinai Medical Center, Smidt Heart Institute, Los Angeles, CA, USA.

Background: Depression is prevalent in patients with heart failure and after heart transplant. We identified the prevalence of pre- and post-transplant depression and its association with clinical characteristics and post-transplant outcomes.

Methods: We reviewed 114 adults transplanted 1/1/2015 to 12/31/2015 and identified patients with pre- and post-transplant depression. Clinical characteristics and outcomes were compared.

Results: Of 114 patients, 35.1% had pre-transplant depression and 26.3% had post-transplant depression. Patients with post-transplant depression within the first year were significantly more likely to have acute rejection (10% vs 0%), longer intensive care unit (11.7 days vs 7.8 days) and hospital stay (31.7 days vs 16.3 days), and discharge to inpatient rehabilitation (26.7% vs 8.3%). Patients with post-transplant depression within the first year had significantly higher 5-year mortality (30% vs 9.5%, p = .009). However, after adjustment for total artificial heart/biventricular assist device, acute rejection, intensive care unit, and hospital length of stay, this relationship was no longer significant (HR 2.11; 95% CI 0.18-25.27; p = .556).

Conclusions: Depression is common among heart transplant candidates and recipients. While pre-transplant depression did not impact outcomes, patients with post-transplant depression were more likely to have had a complicated course, suggesting the need for increased vigilance regarding depression in such patients.
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http://dx.doi.org/10.1111/ctr.14204DOI Listing
March 2021

Crossing low/moderate-level donor-specific antibodies during heart transplantation.

Clin Transplant 2021 03 30;35(3):e14196. Epub 2020 Dec 30.

Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Donor-specific antibodies (DSAs) in patients prior to heart transplantation are associated with increased risk of rejection and can lead to longer waitlist times, but it is not known whether patients with low/moderate-level DSA at transplant have acceptable post-transplant outcomes. We performed a single-center, retrospective review to examine outcomes associated with crossing pre-existing low/moderate-level DSA. We assessed 864 patients awaiting heart transplantation between 2010 and 2018, identified 67 patients with low/moderate-level DSA and compared them to patients who were sensitized without DSA at the time of heart transplantation, as well as a control group of non-sensitized patients. Outcomes included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE), and 1-year freedom from rejection. In the first-year post-transplant, there was decreased freedom from antibody-mediated rejection (AMR) in the patients with pre-existing DSA compared with patients sensitized without DSA and non-sensitized patients. However, the DSA group experienced similar 3-year post-transplant survival, freedom from CAV, and freedom from NF-MACE compared with the other study groups. Our findings suggest that crossing low/moderate-level DSA does not lead to worse outcomes in heart transplantation and may offer a viable way to increase a sensitized patient's chance to obtain a suitable donor.
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http://dx.doi.org/10.1111/ctr.14196DOI Listing
March 2021

Acute appendicitis is associated with appendiceal microbiome changes including elevated levels.

BMJ Open Gastroenterol 2020 06;7(1)

Medically Associated Science and Technology (MAST) Program, Cedars-Sinai Medical Center, Los Angeles, California, USA

Objectives: To compare the appendiceal microbiomes and examine the prevalence of species in the appendices of adult subjects with confirmed acute non-perforated appendicitis and controls with healthy appendices.

Design: Archived samples of formalin-fixed paraffin-embedded appendiceal tissues were obtained from 50 consecutive female subjects who underwent appendectomy for acute, non-perforated appendicitis, and 35 consecutive female controls who underwent incidental appendectomy during gynaecological surgery.

Results: 16S rRNA gene sequencing revealed that the relative abundances (RAs) of the major phyla in appendiceal tissues (Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria) were similar in both groups. Beta diversity was significantly different due to differences in Bacteroidetes and Proteobacteria (p<0.0001). Within Proteobacteria, RAs of classes Alphaproteobacteria (~21%, fold change (FC)=1.31, false discovery rate (FDR) p value=0.03) and Epsilonproteobacteria (~1%, FC=0.25, FDR p value>0.05) were increased in acute appendicitis samples. RAs of unknown genera from families Burkholderiaceae and Enterobacteriaceae were decreased in appendicitis samples, and 14 genera were increased, including , and . Quantitative PCR revealed that levels of DNA, but not other species or pathogens tested, were significantly higher in appendicitis samples than in controls (p=0.013). Using a cut-off of 0.31 pg/µL, 40% of appendicitis cases and 6% of controls were positive for , indicating specificity of 93.7% (95% Cl 79.2 to 99.2), sensitivity of 40.9% (95% Cl 24.7 to 54.5), and OR of 10.38 (Fisher's p value=0.0006, 95% Cl 2.3 to 47.4).

Conclusions: Our findings indicate that may be a significant cause of acute appendicitis. This supports earlier studies and suggests that targeted antibiotic therapies could be an alternative treatment for a subset of non-complicated acute appendicitis cases.
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http://dx.doi.org/10.1136/bmjgast-2020-000412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279619PMC
June 2020

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort.

Sci Rep 2020 01 21;10(1):867. Epub 2020 Jan 21.

Medically Associated Science and Technology (MAST) program, Department of Medicine, Cedars-Sinai, Los Angeles, 90048, USA.

There is no clear study identifying the microbiome of the appendix. However, in other diverticular conditions, such as diverticulosis, methanogens appear important. We investigated whether patients who had undergone appendectomies had decreased levels of exhaled methane (CH). Consecutive patients who underwent breath testing (BT) from November 2005 to October 2013 were deterministically linked to electronic health records. The numbers of patients with CH ≥ 1 ppm (detectable) and ≥ 3 and ≥ 10 ppm (excess) were compared between patients who did and did not undergo appendectomy using a multivariable model adjusted for age and sex. Of the 4977 included patients (48.0 ± 18.4 years, 30.1% male), 1303 (26.2%) had CH ≥ 10 ppm, and 193 (3.9%) had undergone appendectomy. Appendectomy was associated with decreased odds of CH ≥ 1, ≥ 3, and ≥ 10 ppm (ORs (95% CI) = 0.67 (0.47-0.93), p = 0.02; 0.65 (0.46-0.92), p = 0.01; and 0.66 (0.46-0.93), p = 0.02, respectively). Additionally, the percentage of CH producers increased 4-fold from the first to ninth decade of life. This is the first study to report that appendectomy is associated with decreased exhaled CH. The appendix may play an active physiologic role as a reservoir of methanogens.
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http://dx.doi.org/10.1038/s41598-020-57662-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972888PMC
January 2020

Obesity, diabetes, and the gut microbiome: an updated review.

Expert Rev Gastroenterol Hepatol 2019 Jan 13;13(1):3-15. Epub 2018 Nov 13.

a Medically Associated Science and Technology (MAST) Program , Cedars-Sinai Medical Center , Los Angeles , CA , USA.

Introduction: Obesity and diabetes are two of the most prevalent health problems and leading causes of death globally. As research on the intestinal microbiome increases, so does our understanding of its intricate relationship to these diseases, although this has yet to be fully elucidated. Areas covered: This review evaluates the role of the gut microbiome in obesity and diabetes, including the influences of internal and environmental factors. Literature searches were performed using the keywords 'diabetes,' 'insulin resistance,' 'gut microbiome,' 'gut microbes,' 'obesity,' and 'weight gain.' Expert commentary: Highlights of recent research include new findings regarding the effects of caloric restriction, which expound the importance of diet in shaping the gut microbiome, and studies reinforcing the lasting implications of antibiotic use for diabetes and obesity, particularly repeated doses in early childhood. Mechanistically, interactions between the microbiome and the host innate immune system, mediated by TLR4-LPS signaling, have been shown to meditate the metabolic benefits of caloric restriction. Further, gut microbes haven now been shown to regulate oxygen availability via butyrate production, thus protecting against the proliferation of pathogens such as E. coli and Salmonella. However, many microbial metabolites remain unidentified and their roles in obesity and diabetes remain to be determined.
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http://dx.doi.org/10.1080/17474124.2019.1543023DOI Listing
January 2019
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