Transplantation Direct August 2021 Issue

JUST RELEASED - TRANSPLANTATION DIRECT - AUGUST ISSUE

The August issue of Transplantation Direct is online. This is an issue touching many areas of the transplantation field, including kidney, liver, lung, heart, intestinal, bone marrow and stem cell transplantation, as well as xenotransplantation. We offer reviews on monoclonal gammopathy of undetermined significance in kidney transplantation (Tx) and on protocols for anonymous living liver donation. There are articles on the topic on normothermic perfusion of DCD kidneys -- one relates to GWAS of key mitochondrial pathways in pig studies, and the other on regional organ perfusion programs. Another article looks at the effect of nephron mass in DCD kidneys regarding pediatric donation to adults. The subjects of other kidney Tx studies include HLA incompatible transplantation in sensitized patients, the impact of Mayo Adhesive Probability score in living donor transplantation, transplanting patients with pre-Tx pulmonary hypertension, outcomes in patients receiving dual basiliximab and ATG induction, and the association of HLA alleles with post-Tx diabetes. Liver transplant articles touch on allograft dysfunction related to DCD vs DBD grafts, long-term results from a prolonged-release tacrolimus trial, desensitizing recipients with preformed DSA, surgical aspects of interposition grafts for split livers, and transplanting organs from a SARS-CoV-2 positive living donors. Other topics relate to biomarkers for restrictive allograft syndrome after lung Tx, veno-arterial ECMO to bridge heart Tx, GvHD after intestinal Tx, and long-term effects of ABO mismatching on stem cell Tx. For those interested in xenotransplantation, mechanisms of neutrophil-induced tissue damage are explored. To unpack all the details, please visit our open access Transplantation Direct website.

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Hot Off The Press

«HOT OFF THE PRESS»
RECENT PUBLICATIONS IDENTIFIED
BY TTS EDUCATION COMMITTEE ON COVID-19

Selected Publications by TTS Education Committee. This week's selection made by Dr. Enver Akalin.

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

Meagan P. O’Brien et al.
New England Journal of Medicine; August 4, 2020. DOI: 10.1056/NEJMoa2109682

This study randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted.

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Antibody Response After a Third Dose of the mRNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses

Ilies Benotmane et al.
JAMA. 2021 Jul 23. doi: 10.1001/jama.2021.12339.PMID: 34297036

One month after the second dose, 159 kidney transplant recipients had IgG levels less than 50 AU/mL. Ninety-five patients (59.7%) had no antibody response after 2 doses and 64 patients (40.3%) showed a response below the positivity limit (titers, 6.8-49.9 AU/mL). The third dose was injected a median of 51 days (IQR, 48-59 days) after the second dose. The antibody response was measured a median of 28 days (IQR, 27-33 days) after the third vaccine injection, and 78 patients (49%) had antibody levels greater than 50 AU/mL (median antibody titers of responders, 586 AU/mL; IQR, 197.2-1920.1 AU/mL. Patients who had a weak response after the second dose were more likely to develop an antibody response after the third dose compared with those without an antibody response (81.3% vs 27.4%, respectively). Patients taking tacrolimus, mycophenolate, and steroids were less likely to develop anti–SARS-CoV-2 antibodies than those treated with other regimens (35% vs 63%, respectively).

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Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

The REMAP-CAP, ACTIV-4a, and ATTACC Investigators
New England Journal of Medicine; August 4, 2021 DOI: 10.1056/NEJMoa2103417

In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.

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TTS Masterclasses: Outcome Reporting Series Begins August 18

TTS Members can now register for FREE for the last two Masterclass Series on Transplant Immunology and Outcome Reporting. Members must pre-register to attend the live Masterclasses.

TTS is pleased to announce that the remaining two Masterclass Series (Transplant Immunology Series & Outcome Reporting Series) have been granted European CME credits (ECMEC®s) by the European Accreditation Council for Continuing Medical Education (EACCME®).

Attendance at the live Masterclasses is mandatory to receive the certificate.

Upcoming Masterclasses

Masterclasses

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Upcoming August 18 TID-TTS Webinar

August 18, 2021

09:00 (-4 GMT - Montreal time)

Join the discussion on solid organ transplant recipient with post-transplant central nervous system (CNS) infection. Our panel will discuss the differential diagnoses and the diagnostic approaches including novel microbiologic tests. Click button below for details and local times.

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