Venous vascular reconstruction of a robotically procured right kidney with two renal veins transplanted into a pediatric recipient.

BACKGROUND: Right versus left kidney donor nephrectomy remains a controversial topic in renal transplantation given the increased incidence of right kidney vascular anomalies and associated venous thrombosis. We present the case of a 3-year-old pediatric recipient with urethral atresia and end-stage kidney disease who received a robotically procured living donor right pelvic kidney with two short same-size renal veins and a short ureter. METHODS: We utilized a completely deceased iliac vein system (common iliac vein with both external and internal veins) to extend the two renal veins. Due to the distance between both renal veins, the external iliac vein was anastomosed to the upper hilum renal vein, and the internal iliac vein was anastomosed to the lower hilum renal vein. The donor's short ureter was anastomosed to the recipient's ureter end-to-side. RESULTS: The patient had immediate graft function and there were no post-operative complications. Renal ultrasound was unremarkable at 48 hours post-transplant. Serum creatinine was 0.5 mg/dL at 3 months post-transplant. CONCLUSION: We demonstrate the successful transplantation of a robotically procured right pelvic donor kidney with two short renal veins using a deceased donor iliac vein system for venous reconstruction without increasing technical complications. This technique of venous reconstruction can be used in right kidneys with similar anatomical variations without affecting graft function.

Innovative surgical techniques in the intestine and multivisceral transplant.

PURPOSE OF REVIEW: This timely review delves into the evolution of multivisceral transplantation (MVT) over the past six decades underscoring how advancements in surgical techniques and immunosuppression have driven transformation, to provide insight into the historical development of MVT, shedding light on its journey from experimentation to a valuable clinical approach. RECENT FINDINGS: The review presents contemporary enhancements in surgical methods within the context of intestinal transplantation. The versatility of MVT is emphasized, accommodating diverse organ combinations and techniques. Both isolated intestinal transplantation (IIT) and MVT have seen expanded indications, driven by improved parenteral nutrition, transplantation outcomes, and surgical innovations. Surgical techniques are tailored based on graft type, with various approaches for isolated transplantation. Preservation strategies and ostomy techniques are also covered, along with graft assessment advancements involving donor-specific antibodies. SUMMARY: This review's findings underscore the remarkable evolution of MVT from experimental origins to a comprehensive clinical practice. The progress in surgical techniques and immunosuppression has broadened the spectrum of patients who can benefit from intestinal transplant, including both IIT and MVT. The expansion of indications offers hope to patients with complex gastrointestinal disorders. The detection of donor-specific antibodies in graft assessment advances diagnostic accuracy, ultimately improving patient outcomes.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event - Two acute cellular rejection examples in intestinal transplantation.

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

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.

Xenoreactive antibodies in α-granules of human platelets bind pig liver endothelial cells.

Pig liver xenotransplantation is limited by a thrombocytopenic coagulopathy that occurs immediately following graft reperfusion. In vitro and ex vivo studies from our lab suggested that the thrombocytopenia may be the result of a species incompatibility in platelet glycosylation. Realization that platelet α-granules contain antibodies caused us to reevaluate whether the thrombocytopenia in liver xenotransplantation could occur because IgM and IgG from inside platelet α-granules bound to pig liver sinusoidal endothelial cells (LSECs). Our in vitro analysis of IgM and IgG from inside α-granules showed that platelets do carry xenoreactive antibodies that can bind to known xenoantigens. This study suggests that thrombocytopenia occurring following liver xenotransplantation could occur because of xenoreactive antibodies tethering human platelets to the pig LSEC enabling the platelet to be phagocytosed. These results suggest genetic engineering strategies aimed at reducing xenoantigens on the surface of pig LSEC will be effective in eliminating the thrombocytopenia that limits survival in liver xenotransplantation.

Cut-off points in the waist:height ratio for the prediction of insulin resistance, second stage of sexual maturation in Brazilian adolescents.

The objective of this study was verify the best waist:height ratio (WHtR) cut-off points for the prediction of insulin resistance (IR) according to stage of sexual maturation in Brazilian adolescents. Data were analysed from 37 759 adolescents between 12 and 17 years of age, of both sexes, participating in the ERICA study on cardiovascular risk factors in adolescents ('Estudo de Riscos Cardiovasculares em Adolescentes - ERICA'). The following variables were included sex, age and sexual maturity according to the Tanner stage, waist circumference, height, WHtR, fasting insulin and fasting blood sugar so as to obtain the homeostasis model assessment-estimated insulin resistance (HOMA-IR). We constructed an Receiver Operating characteristic (ROC) curve for each group in order to determine the best WHtR cut-off points for the sample stratified by sex and stratified by sex and sexual maturation stage. The female sex corresponded to 60% of the sample, with a mean age of 14·7 years (sd ± 0·08 years) and 13·1 % had IR. The prediction of IR through the WHtR indicator was better for boys, where all the areas under the ROC curve were superior to 0·70. When stratifying by sex alone, the best WHtR cut-off points found were equal to 0·45 for girls and 0·44 for boys. When stratifying by Tanner maturation stages, the cut-off points were reduced with advancing sexual maturation in the male group, while the opposite occurred in the female group. Among Brazilian adolescents, WHtR is a good predictor of IR evaluated by HOMA-IR, but different cut-off points should be adopted according to sex and sexual maturation stage.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Clinical characteristics and outcomes in CMV infection in intestinal transplant recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.

Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.

Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

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.

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.

Creating a Single Inflow Orifice From Living Donor Kidney Allografts With Multiple Renal Arteries.

Background: Multiple renal arteries (MRA) are often encountered during living-donor kidney transplantation (LDKT), requiring surgeons to pursue complex renovascular reconstructions prior to graft implantation. With improvements in reconstruction and anastomosis techniques, allografts with MRA can be successfully transplanted with similar outcomes to allografts with a single renal artery. Here, we describe in detail various surgical techniques for reconstruction of MRA grafts with the intent of creating a single arterial inflow. Methods: We retrospectively reviewed the medical records of all LDKT recipients with laparoscopically procured MRA kidneys between March 2008 and July 2021. Recipient and donor characteristics, operative data, type of reconstruction, and recipient outcomes were analyzed. The primary outcomes were the incidence of developing delayed graft function (DGF) and/or a vascular or urological complication within 12 months post-transplant. Results: Seventy-three LDKT recipients of MRA donor allografts were evaluated. Two renal arteries (RA) were encountered in 62 allografts (84.9%) and three RA in 11 allografts (15.1%). Renal artery reconstruction was performed in 95.8% (70/73) of patients. Eighteen different reconstruction techniques of MRA were utilized, the most common being side-to-side anastomosis in allografts with two RA (N = 44) and side-to-side-to-side anastomosis in allografts with three RA (N = 4). Interposition grafting was performed in seven cases (9.6%). A single ostium was created in 69 cases (94.5%), and the median warm ischemia time was 27 (range 20-42) minutes. None of the patients developed DGF or post-operative vascular or urological complications. Median creatinine at 3, 6, and 12 months post-transplant remained stable at 1.1 mg/dl. With a median follow-up of 30.4 months post-transplant, only one graft failure has been observed-death-censored graft survival was 98.6%. Conclusion: Complex reconstruction techniques to create a single renal artery ostium for graft implantation anastomosis in allografts with MRA show acceptable warm ischemic times, with no increased risk of post-operative vascular or urological complications.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.

En-Bloc Simultaneous Heart-Liver Transplantation in Adult Patients.

INTRODUCTION: Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique. METHODS: Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection. RESULTS: Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications. CONCLUSION: En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.

Anti-C5 Antibody Tesidolumab Reduces Early Antibody-mediated Rejection and Prolongs Survival in Renal Xenotransplantation.

OBJECTIVE: Pig-to-primate renal xenotransplantation is plagued by early antibody-mediated graft loss which precludes clinical application of renal xenotransplantation. We evaluated whether temporary complement inhibition with anti-C5 antibody Tesidolumab could minimize the impact of early antibody-mediated rejection in rhesus monkeys receiving pig kidneys receiving costimulatory blockade-based immunosuppression. METHODS: Double (Gal and Sda) and triple xenoantigen (Gal, Sda, and SLA I) pigs were created using CRISPR/Cas. Kidneys from DKO and TKO pigs were transplanted into rhesus monkeys that had the least reactive crossmatches. Recipients received anti-C5 antibody weekly for 70 days, and T cell depletion, anti-CD154, mycophenolic acid, and steroids as baseline immunosuppression (n = 7). Control recipients did not receive anti-C5 therapy (n = 10). RESULTS: Temporary anti-C5 therapy reduced early graft loss secondary to antibody-mediated rejection and improved graft survival (P < 0.01). Deleting class I MHC (SLA I) in donor pigs did not ameliorate early antibody-mediated rejection (table). Anti-C5 therapy did not allow for the use of tacrolimus instead of anti-CD154 (table), prolonging survival to a maximum of 62 days. CONCLUSION: Inhibition of the C5 complement subunit prolongs renal xenotransplant survival in a pig to non-human primate model.