The Seattle Heart Failure Model in Kidney Transplant Recipients.

Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.

Impact of Renal Replacement Therapy on Rejection among Liver Transplant Recipients.

Introduction: Renal dysfunction in liver transplant recipients is associated with an increased risk of morbidity and mortality, with an even higher risk among patients requiring renal replacement therapy. There is limited data evaluating rejection outcomes in patients requiring renal replacement therapy after liver transplant. Program evaluation aims: To evaluate the incidence of biopsy-proven acute rejection, recipient and graft survival, infection, renal dysfunction, and immunosuppression practices. Design: This was a single-center, retrospective, cohort study. To be eligible, patients were deceased donor liver transplant recipients ≥18 year of age transplanted between January 2017 and August 2019 who received steroid-only induction and tacrolimus as part of their initial immunosuppression regimen. Results: Recipients that required renal replacement therapy (N = 86) were compared to those who received no renal replacement therapy (N = 158). Biopsy-proven acute rejection at 1-year posttransplant was significantly higher among those requiring renal replacement therapy (36% vs 13%, P < .001). Patient survival at 12 months was 77% for those requiring renal replacement therapy and 94% for those not requiring renal replacement therapy (P < .001). Infection (HR 3.8, 95% CI 1.6-8.8; P < .001), but not rejection (HR 0.7, 95% CI 0.3-1.7; P = .5) was an independent predictor of mortality. The use of renal replacement therapy after liver transplant necessitated careful titration of immunosuppression to balance the detrimental risks of infection versus rejection in this high-risk population.

Persistence of long-term insulin independence after islet transplantation and two subsequent pregnancies.

Pregnancy increases metabolic demand for insulin and may lead to the exhaustion of intraportally transplanted islets and post-gestational hyperglycemia. To prevent these complications, we implemented preemptive insulin supplementation during two subsequent pregnancies in an insulin-independent islet transplant recipient. This strategy resulted in optimal blood glucose control during the pregnancies, the preservation of the optimal islet graft function and the postpartum maintenance of long-term insulin independence.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

The Accuracy of Nonstandardized MELD/PELD Score Exceptions in the Pediatric Liver Allocation System.

BACKGROUND: In the United States, over half of pediatric candidates receive exceptions and status upgrades that increase their allocation model of end-stage liver disease/pediatric end-stage liver disease (MELD/PELD) score above their laboratory MELD/PELD score. We determined whether these "nonstandardized" MELD/PELD exceptions accurately depict true pretransplant mortality risk. METHODS: Using data from the Scientific Registry of Transplant Recipients, we identified pediatric candidates (<18 y of age) with chronic liver failure added to the waitlist between June 2016 and September 2021 and estimated all-cause pretransplant mortality with mixed-effects Cox proportional hazards models that treated allocation MELD/PELD and exception status as time-dependent covariates. We also estimated concordance statistics comparing the performance of laboratory MELD/PELD with allocation MELD/PELD. We then compared the proportion of candidates with exceptions before and after the establishment of the National Liver Review Board. RESULTS: Out of 2026 pediatric candidates listed during our study period, 403 (19.9%) received an exception within a week of listing and 1182 (58.3%) received an exception before delisting. Candidates prioritized by their laboratory MELD/PELD scores had an almost 9 times greater risk of pretransplant mortality compared with candidates who received the same allocation score from an exception (hazard ratio 8.69; 95% confidence interval, 4.71-16.03; P < 0.001). The laboratory MELD/PELD score without exceptions was more accurate than the allocation MELD/PELD score with exceptions (Harrell's c-index 0.843 versus 0.763). The proportion of patients with an active exception at the time of transplant decreased significantly after the National Liver Review Board was implemented (67.4% versus 43.4%, P < 0.001). CONCLUSIONS: Nonstandardized exceptions undermine the rank ordering of pediatric candidates with chronic liver failure.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

The Impact of Treatment Delay on Hepatitis C Liver Transplant Outcomes.

Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists' roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4-6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.

Review Paper on Penetrating Brain Injury: Ethical Quandaries in the Trauma Bay and Beyond.

OBJECTIVE: The aim of this review was to review the ethical and multidisciplinary clinical challenges facing trauma surgeons when resuscitating patients presenting with penetrating brain injury (PBI) and multicavitary trauma. BACKGROUND: While there is a significant gap in the literature on managing PBI in patients presenting with multisystem trauma, recent data demonstrate that resuscitation and prognostic features for such patients remains poorly described, with trauma guidelines out of date in this field. METHODS: We reviewed a combination of recent multidisciplinary evidence-informed guidelines for PBI and coupled this with expert opinion from trauma, neurosurgery, neurocritical care, pediatric and transplant surgery, surgical ethics and importantly our community partners. RESULTS: Traditional prognostic signs utilized in traumatic brain injury may not be applicable to PBI with a multidisciplinary team approach suggested on a case-by-case basis. Even with no role for neurosurgical intervention, neurocritical care, and neurointerventional support may be warranted, in parallel to multicavitary operative intervention. Special considerations should be afforded for pediatric PBI. Ethical considerations center on providing the patient with the best chance of survival. Consideration of organ donation should be considered as part of the continuum of patient, proxy and family-centric support and care. Community input is crucial in guiding decision making or protocol establishment on an institutional level. CONCLUSIONS: Support of the patient after multicavitary PBI can be complex and is best addressed in a multidisciplinary fashion with extensive community involvement.

Rodent Brain Tumor Models for Studies Focusing on Boron Neutron Capture Therapy.

Rodent brain tumor models have been very useful in advancing the treatment of glioblastomas. This review focuses on the four most widely used rodent brain tumor models: the C6, 9L, and F98 rat gliomas, and the GL261 murine glioma. All of these have been used in studies relating to boron neutron capture therapy. The most important of these studies were those using the 9L gliosarcoma, which led to the clinical use of boronophenylalanine, and the F98 glioma, which has been used for the preclinical evaluation of new boron delivery agents and methods of optimizing their delivery.

Impact of Steroid Only Induction on Rejection in Simultaneous Liver-Kidney Transplantation.

Introduction: The occurrence of simultaneous liver kidney transplantation has greatly increased; however, the ideal induction and maintenance immunosuppression remains unknown. Question: This evaluation aimed to determine if corticosteroid only induction in simultaneous liver kidney transplant recipients provided adequate prophylaxis against rejection when compared to basiliximab. Design: This was a single center, retrospective, cohort study of adult simultaneous liver kidney transplant recipients from June 2010 to June 2019 receiving corticosteroid only (N = 41) or basiliximab (N = 42) induction. Results: Liver or kidney biopsy proven acute rejection at 3 months was comparable between the corticosteroid only and basiliximab groups (10% vs 7%, P = .67), which persisted through 12 months posttransplant (15% vs 21%, P = .42). The occurrence of any infection at 3 months was increased in the corticosteroid only group relative to the basiliximab group (41% vs 21%, P = .049). Graft and patient survival at 12 months were similar between groups. Maintenance immunosuppression was overall minimized with a tacrolimus goal of 6-8 ng/mL, mycophenolate mofetil dose reduction to 1000 mg/day by 3 months, and early steroid withdrawal in both groups. Conclusion: Our findings suggested that corticosteroid only induction was an effective strategy for preventing rejection in simultaneous liver kidney transplant recipients, even in combination with reduced maintenance immunosuppression.

The Effect of Normothermic Machine Perfusion on the Immune Profile of Donor Liver.

Background: Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP. Methods: Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student's t-test. Results: Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion. Conclusions: Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.

Which cava anastomotic techniques are optimal regarding immediate and short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations.

BACKGROUND: It has long been debated whether cava anastomosis should be performed with the piggyback technique or cava replacement, with or without veno-venous bypass (VVB), with or without temporary portocaval shunt (PCS) in the setting of liver transplantation. OBJECTIVES: To identify whether different cava anastomotic techniques and other maneuvers benefit the recipient regarding short-term outcomes and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021240979). RESULTS: Of 3205 records screened, 307 publications underwent full-text assessment for eligibility and 47 were included in qualitative synthesis. Four studies were randomized control trials. Eighteen studies were comparative. The remaining 25 were single-center retrospective noncomparative studies. CONCLUSION: Based on existing data and expert opinion, the panel cannot recommend one cava reconstruction technique over another, rather the surgical approach should be based on surgeon preference and center dependent, with special consideration toward patient circumstances (Quality of evidence: Low | Grade of Recommendation: Strong). The panel recommends against routine use of vevo-venous bypass (Quality of evidence: Very Low | Grade of Recommendation: Strong) and against the routine use of temporary porto-caval shunt (Quality of evidence: Very Low | Grade of Recommendation: Strong).

Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research.

Rodent brain tumor models have been useful for developing effective therapies for glioblastomas (GBMs). In this review, we first discuss the 3 most commonly used rat brain tumor models, the C6, 9L, and F98 gliomas, which are all induced by repeated injections of nitrosourea to adult rats. The C6 glioma arose in an outbred Wistar rat and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma arose in a Fischer rat and is strongly immunogenic, which must be taken into consideration when using it for therapy studies. The F98 glioma may be the best of the 3 but it does not fully recapitulate human GBMs because it is weakly immunogenic. Next, we discuss a number of mouse models. The first are human patient-derived xenograft gliomas in immunodeficient mice. These have failed to reproduce the tumor-host interactions and microenvironment of human GBMs. Genetically engineered mouse models recapitulate the molecular alterations of GBMs in an immunocompetent environment and "humanized" mouse models repopulate with human immune cells. While the latter are rarely isogenic, expensive to produce, and challenging to use, they represent an important advance. The advantages and limitations of each of these brain tumor models are discussed. This information will assist investigators in selecting the most appropriate model for the specific focus of their research.

hEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.

INTRODUCTION: Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti-pig antibody binding (α-1,3-galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO-1]), and a self-recognition receptor (integrin-associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena. METHODS: Livers from GaltKO.hCD46 pigs ("2-gene," n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO-1 ("6-gene," n = 4) were perfused ex vivo with whole human blood. Six-gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively. RESULTS: The average perfusion times increased from 304 (±148) min in the 2-gene group to 856 (±61) min in the 6-gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2-gene to 1354 U/h in the 6-gene group (p = .047). Platelet sequestration tended to be delayed in the 6-gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6-gene group (p = .058). CONCLUSIONS: The combination of the hEPCR.hTBM.hCD47.hHO-1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.

Ischemic Cholangiopathy Postdonation After Circulatory Death Liver Transplantation: Donor Hepatectomy Time Matters.

BACKGROUND: Outcomes of liver transplantation (LT) from donation after circulatory death (DCD) have been improving; however, ischemic cholangiopathy (IC) continues to be a problem. In 2014, measures to minimize donor hepatectomy time (DHT) and cold ischemic time (CIT) have been adopted to improve DCD LT outcomes. METHODS: Retrospective review of all patients who underwent DCD LT between 2005 and 2017 was performed. We compared outcomes of patients who were transplanted before 2014 (historic group) with those who were transplanted between 2014 and 2017 (modern group). RESULTS: We identified 112 patients; 44 were in the historic group and 68 in the modern group. Donors in the historic group were younger (26.5 versus 33, P = 0.007) and had a lower body mass index (26.2 versus 28.2, P = 0.007). DHT (min) and CIT (h) were significantly longer in the historic group (21.5 versus 14, P < 0.001 and 5.3 versus 4.2, P < 0.001, respectively). Fourteen patients (12.5%) developed IC, with a significantly higher incidence in the historic group (23.3% versus 6.1%, P = 0.02). There was no difference in graft and patient survival between both groups. CONCLUSION: In appropriately selected recipients, minimization of DHT and CIT may decrease the incidence of IC. These changes can potentially expand the DCD donor pool.

Acute on Chronic Liver Failure: Factors Associated With Transplantation.

Acute on chronic liver failure (ACLF) carries a poor prognosis unless liver transplantation is offered. We present risk factors associated with proceeding with liver transplantation in patients with ACLF. METHODS: A retrospective review of all patients with ACLF who presented to a single transplant center between January 2016 and December 2017 was performed. We compared patients who were transplanted with patients who were not. RESULTS: During the study period, 144 patients with ACLF were identified, 86 patients (59.7%) were transplanted, and 58 were not. The transplanted patients had a lower number of failed organs (4 versus 5, P < 0.001) and lower incidence of ACLF grade 3 (76.7% versus 94.8%, P = 0.014) compared with nontransplanted patients. Liver transplantation offered a 1-y survival of 86% as compared to 12% in the nontransplanted group. Hospital charges were significantly higher among transplanted patients as compared with the nontransplanted patients ($227 886 versus $88 900, P < 0.001). Elevated serum lactate was a risk factor in not offering liver transplantation in ACLF patients. CONCLUSIONS: In appropriately selected patients with ACLF, liver transplantation is feasible and can provide above 86% 1-y patient survival even in grade 3 ACLF.

The Impact of COVID-19 on Kidney Transplant Recipients in Pre-Vaccination and Delta Strain Era: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

A Comparison of the Clinical, Viral, Pathologic, and Immunologic Features of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus 2019 (COVID-19) Diseases.

CONTEXT.­: The purpose of this review was to compare 3 coronavirus diseases, including severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses, respectively. OBJECTIVE.­: To cover the following topics: clinical considerations, viral characteristics, pathology, immune response, pathogenesis, and the prognosis associated with each coronavirus disease in humans. DATA SOURCES.­: Clinically, flu-like symptoms are usual at the time of presentation for all 3 diseases, but these vary from asymptomatic to severe multisystem involvement. The pathology associated with symptomatic severe acute respiratory syndrome and COVID-19 has been well described, the most prominent of which is diffuse alveolar damage. The immune response to each of these viruses is highly complex and includes both humoral and cellular components that can have a significant impact on prognosis. In severe cases of COVID-19, a dysregulated innate host immune system can initiate a hyperinflammatory syndrome dominated by endothelial dysfunction that can lead to a hypercoagulable state with microthrombi, resulting in a systemic microvascular and macrovascular disease. CONCLUSIONS.­: The severe acute respiratory syndrome and Middle East respiratory syndrome epidemics have been limited, involving approximately 8000 and 2500 individuals, respectively. In contrast, COVID-19 has resulted in a worldwide pandemic with more than 177 million cases and 3.9 million deaths as of June 15, 2021, and fatality rates ranging from less than 0.1% to approximately 10% depending upon the country. Ending on a positive note, the development of a number of vaccines, at least 6 of which now are in clinical use, should mitigate and eventually control the devastating COVID-19 pandemic.