Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanità–ISS) reported the first autochthonous case of infection, a dedicated surveillance system for ...SARS‐CoV‐2‐positive (COVID+) cases has been created in Italy. These data were cross‐referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS‐COV‐2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non‐SOTRs) with follow‐up through September 30, 2020. The CI of SARS‐CoV‐2 infection in SOTRs was 1.02%, higher than in COVID+ Non‐SOTRs (0.4%, p < .05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio IRR 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60‐day CI of mortality was 30.6%, twice as much that of COVID+ Non‐SOTRs (15.4%) with a 60‐day gender and age adjusted odds ratio (adjusted‐OR) of 3.83 for COVID+ SOTRs (95% confidence interval 3.03–4.85). The lowest 60‐day adjusted‐OR was observed in liver SOTRs (OR 0.46, 95% confidence interval 0.25–0.86). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID‐19.
In Italy, SARS‐CoV‐2 infection risk for solid organ recipients compared to the general population is two times higher and mortality risk is four times higher, with heart recipients at the highest risk of infection and liver recipients at the lowest risk of both infection and mortality.
Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of ...diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.
Mortality among patients hospitalized for COVID‐19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from ...a multicenter registry of SOTR hospitalized for COVID‐19, we compared 28‐day mortality between early 2020 (March 1, 2020–June 19, 2020) and late 2020 (June 20, 2020–December 31, 2020). Multivariable logistic regression was used to assess comorbidity‐adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28‐day mortality decreased between the early and late periods (112/571 19.6% vs. 55/402 13.7%) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46–0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 10.9% vs. 243/402 61.5%, p < .001 and 50/571 8.8% vs. 213/402 52.2%, p < .001, respectively), and the use of hydroxychloroquine and IL‐6/IL‐6 receptor inhibitor decreased (329/571 60.0% vs. 4/492 1.0%, p < .001 and 73/571 12.8% vs. 5/402 1.2%, p < .001, respectively). Mortality among SOTR hospitalized for COVID‐19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.
Data from the pre‐vaccine era show declining mortality among solid organ transplant recipients hospitalized for COVID‐19 over the course of the pandemic. Kalil comments on page 12.
In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer ...(CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;Kras
;Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5
stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.
Objective:
We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to ...stratify the results by route of administration, disease, treatment dose, and duration.
Methods:
We searched seven electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science, and CINAHL/Academic Search Premier) in February 2014 to identify potentially relevant studies. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible.
Results:
We included 74 articles with a total of 3753 participants. Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration (95% confidence interval CI, 0.5–28.9) to 52.2% for intra-articular administration (95% CI, 40.5–63.6). Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8–12.0) to 60.0% for hematological malignancies (95% CI, 38.0–78.6). The risk also varied according to dose from 2.4% (95% CI, 0.6–9.3) (low dose) to 21.5% (95% CI, 12.0–35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3–7.4) (<28 d) to 27.4% (95% CI, 17.7–39.8) (>1 year) in asthma patients.
Conclusions:
1) Adrenal insufficiency after discontinuation of glucocorticoid occurs frequently; 2) there is no administration form, dosing, treatment duration, or underlying disease for which adrenal insufficiency can be excluded with certainty, although higher dose and longer use give the highest risk; 3) the threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation.
Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses to injury and increased immunogenicity, ...thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates with aging and augments immunogenicity. Ischemia reperfusion injury induces a systemic increase of cf-mt-DNA that promotes dendritic cell-mediated, age-specific inflammatory responses. Comparable events are observed clinically, with the levels of cf-mt-DNA elevated in older deceased organ donors, and with the isolated cf-mt-DNA capable of activating human dendritic cells. In experimental models, treatment of old donor animals with senolytics clear senescent cells and diminish cf-mt-DNA release, thereby dampening age-specific immune responses and prolonging the survival of old cardiac allografts comparable to young donor organs. Collectively, we identify accumulating cf-mt-DNA as a key factor in inflamm-aging and present senolytics as a potential approach to improve transplant outcomes and availability.
Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need ...to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage‐specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer‐specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.
This article presents consensus expert opinion transplant recommendations for patients with a prior breast, colorectal, anal, urological, gynecological, or non‐small cell lung cancer. See the companion review on page 475 and an editorial from Hart and Engels on page 447.
To assess long-term survival, graft function, and health-related quality of life (QOL) after visceral transplantation.
Despite continual improvement in early survival, the long-term therapeutic ...efficacy of visceral transplantation has yet to be defined.
A prospective cross-sectional study was performed on 227 visceral allograft recipients who survived beyond the 5-year milestone. Clinical data were used to assess outcome including graft function and long-term survival predictors. The socioeconomic milestones and QOL measures were assessed by clinical evaluation, professional consultation, and validated QOL inventory.
Of 376 recipients, 227 survived beyond 5 years, with conditional survival of 75% at 10 years and 61% at 15 years. With a mean follow-up of 10 ± 4 years, 177 (92 adults, 85 children) are alive, with 118 (67%) recipients 18 years or older. Nonfunctional social support and noninclusion of the liver in the visceral allograft are the most significant survival risk factors. Nutritional autonomy was achievable in 160 (90%) survivors, with current serum albumin level of 3.7 ± 0.5 gm/dL and body mass index of 25 ± 6 kg/m(2). Despite coexistence or development of neuropsychiatric disorders, most survivors were reintegrated to society with self-sustained socioeconomic status. In parallel, most of the psychological, emotional, and social QOL measures significantly (P < 0.05) improved after transplantation. Current morbidities with potential impact on global health included dysmotility (59%), hypertension (37%), osteoporosis (22%), and diabetes (11%), with significantly (P < 0.05) higher incidence among adult recipients.
With new tactics to further improve long-term survival including social support measures, visceral transplantation has achieved excellent nutritional autonomy and good QOL.
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