From the laboratory to the field: how to mitigate pregnancy losses in embryo transfer programs?

Pregnancy losses negatively affect the cattle industry, impacting economic indices and consequently the entire production chain. Early embryonic failure has been an important challenge in the embryo industry because proper identification of embryo death at the beginning of gestation is difficult. This review aimed to provide a better understanding on reproductive failure and the relationship between early embryonic loss and different reproductive biotechniques. This review also considers insights and possible strategies for reducing early embryonic loss. The strategies addressed are as follows: i) great impact of rigorous embryo evaluation on reducing embryo losses; ii) selection of recipients at the time of transfer, taking into account health and nutritional status, and classification of the corpus luteum using ultrasound, either in area or vascularization; and iii) paternal effect as one of the factors that contribute to pregnancy losses, with a focus on embryo transfer.

Surgical complications and technical failure of simultaneous pancreas-kidney transplantation: A 22-year experience from a single center.

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI:  .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.

Directed Organ Donation After Euthanasia.

Organ donation after euthanasia is performed in Belgium, the Netherlands, Canada and Spain. Directed deceased organ donation is currently possible under strict conditions in a limited number of countries, while it is currently not possible to opt for directed donation following euthanasia. While organ donation after euthanasia is a deceased donation procedure, directed organ donation after euthanasia could be seen as a deceased donation procedure with a living donation consent process. Therefore, directed organ donation after euthanasia is feasible on medical and ethical grounds. Strict safeguards should be in place, including the requirement of a pre-existing familial or personal relationship with the proposed recipient, without any evidence of coercion or financial gain.

Subphenotypes of frailty in lung transplant candidates.

Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.

Perioperative mortality in liver transplantation before and after the implementation of the organ allocation policy Share 35.

INTRODUCTION: In 2013, a new liver transplant allocation policy (Share 35) aimed to reduce waitlist-mortality was introduced in the United States. Regional organ sharing for recipients with a MELD score of ≥35 was prioritized over local allocation to those with lower MELD scores. Our aim was to assess the changes in perioperative mortality following the introduction of Share 35 as well as changes in patients' short-term 7-day survival, patients discharged alive and 1-year survival. Analyses were also carried out for the subgroups of patients with MELD scores ≥ and < 35. METHODS: We used data from the Scientific Registry of Transplant Recipients and included liver transplants between March 2002 and December 2018 in this retrospective cohort study. Perioperative mortality was defined as death during and within two days of liver transplant. We used robust interrupted time series analyses to evaluate the impact of Share 35 on mortality. RESULTS: We included 90 002 liver transplants in our analysis and observed a decreasing trend in perioperative mortality over time (-.061 deaths per 1000 cases per month, 95% CI -.084 to -.037, p < .001). Share 35 was not associated with a change in perioperative mortality (p = .33), short-term 7-day survival (p = .48), survival to discharge (p = .56), or 1-year survival (p = .27). CONCLUSIONS: Prioritizing sicker recipients with a MELD score ≥35 for liver transplantation was not associated with a change in postoperative mortality.

Clinical assessment of scannographic markers for sarcopenia in lung transplant candidates.

INTRODUCTION: The selection of patients for lung transplantation is difficult. An aspect of the patient's general condition and frailty can be assessed by measuring the surface area of certain muscles on CT. Indeed, sarcopenia, assessed by measuring the area of psoas muscles on scannographic sections has already been shown to be associated with poor outcomes in lung transplant and other major surgeries and could thus be helpful to evaluate candidates to lung transplant. However, it is not routinely performed by radiologists. As a pilot study, we compared the reliability of computerized tomography scan assessment for sarcopenia by clinicians with that of radiologists. MATERIALS AND METHODS: We conducted a retrospective single-centre study in which preoperative abdominal CT scans of lung transplant patients from 2014 to 2018 were analysed to assess sarcopenia by measuring the surface areas (mm2) of the psoas, paraspinal muscles at the L4 vertebra and diaphragm pillars at the celiac trunk bilaterally. The surfaces were blindly assessed by clinicians and radiologists and the intraclass correlation coefficients between the two measurements were estimated by a generalized linear model using SAS 9.4 software. RESULTS: We performed a double reading of 200 scans. The clinicians 'measurements were comparable to those of the radiologists for the psoas and paraspinal muscles but not for the diaphragm pillars. CONCLUSION: CT measurement of psoas and paraspinal muscle areas by clinicians appears reliable and feasible in routine practice and could be used in the evaluation of lung transplant candidates.

Recipient Comorbidities for Prediction of Primary Graft Dysfunction, Chronic Allograft Dysfunction and Survival After Lung Transplantation.

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992-2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection.

Recipient selection, timing of referral, and listing for lung transplantation.

Recipient selection for lung transplantation is a balance between providing access to transplantation to maximum patients, while utilizing this limited resource in the most optimal way. This review summarizes the current literature and recommendations about referral, listing, and evaluation of lung transplant candidates, with a focus on patients considered to have high risk characteristics.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.

Transplant centers seeking to increase coronavirus disease 2019 (COVID-19) vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.

Removal of the Black race coefficient from the estimated glomerular filtration equation improves transplant eligibility for Black patients at a single center.

Race is a social construct that cannot be measured, can be used imprecisely and may contribute to disparities in kidney transplant access for Black patients. At Beth Israel Deaconess Medical Center, we dropped the Black race coefficient in the estimated glomerular filtration rate (eGFR) report in 2017. We conducted a quality improvement project to examine the impact of this change. Before the change, only 26% of our Black patients were listed for preemptive transplant compared to 70% of White patients. Since the change, we found a steady increase in the percentage of Black patients listed before starting dialysis. The average eGFR at listing prior to 2017 was significantly lower in Black patients but after, there was no longer a significant difference. Nine patients "gained" an average of 457 days of wait time directly related to discarding the Black race coefficient. Increased time on the list prior to dialysis initiation allows for evaluation of potential live donors and improves the possibility of a pre-emptive live or deceased donor transplant and allows for a shorter period on dialysis before transplant. In this single center initiative, we demonstrate the benefit of discarding race from the eGFR report for Black patients awaiting kidney transplantation.

Normal long-term neurologic and graft outcome after liver transplantation in an infant with Neimann-Pick type C disease.

Niemann-Pick type C disease is a rare autosomal recessive lysosomal disorder that leads to the accumulation of lipids in cellular organelles. Affected infants are often cholestatic with hepatosplenomegaly, developmental delay and may present in acute liver failure. Medical therapy has shown some promise in long-term studies, in patients with milder phenotypes of the disease. Liver transplantation has generally not been considered a therapeutic option due to the systemic nature of the condition, and frequent unremitting neurological decline leading to death. We report an infant with multisystem organ failure, and known Niemann-Pick C disease who was successfully transplanted and has maintained normal neurological outcomes now five years after transplantation. We highlight the need for multidisciplinary care in order to recognize different phenotypes that may exist, even in rare diseases, and to be aware of evolving therapeutic options.

A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID-19 pandemic.

INTRODUCTION: Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers. METHODS: Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD > 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019. RESULTS: The retrieval rate for deceased donor livers (71% vs. 54%; P < .0001) and conversion from offer to completed transplant (63% vs. 48%; P < .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort. CONCLUSIONS: We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant.

INTRODUCTION: Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown. METHODS: This single-center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart-review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep. RESULTS: We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025). CONCLUSION: SPPB and chart-review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.

Outcomes of kidney transplant recipients with ESKD due to plasma cell dyscrasia: A case series.

Transplant centers have historically been reluctant to proceed with kidney transplantation in individuals with plasma cell dyscrasias (PCDs) due to concern for high rates of PCD recurrence and PCD-related mortality. As novel therapies for PCDs have improved hematologic outcomes, strategies to optimize kidney transplantation in individuals with PCD-mediated kidney disease are needed. In this single-center case series we discuss our protocol for the transplantation of individuals with ESKD attributed to PCD as well as the hematologic and allograft outcomes of 12 kidney transplant recipients with ESKD attributed to PCD. Median follow-up time after kidney transplantation was 44 months (IQR 36, 84). All patients had a functioning allograft 1 year after kidney transplantation. 9/12 patients were alive and had a functioning allograft 5 years after kidney transplantation. Five patients experienced relapse of PCD (of whom three responded well to subsequent therapies) and four patients developed secondary malignancies, including three patients with urologic malignancies. This case series demonstrates that patients with kidney disease attributed to PCD have favorable outcomes with kidney transplantation. Transplant evaluation in patients with PCDs should involve a multidisciplinary team of transplant nephrologists and oncologists to select appropriate candidates. Providers should consider screening for urologic malignancies pre- and post-transplantation.

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

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.

Pancreas transplantation perceptions and practice: Results from a national US survey.

BACKGROUND: Due to a substantial decline in pancreas transplantation (PT) across the United States over the past 15 years, we sought to understand the perceptions and practices of US PT programs. METHODS: Surveys were sent to members of the American Society of Transplantation Surgeons and the American Society of Transplantation by email and professional society postings between August 2019 and November 2019. RESULTS: One hundred twenty three responses were recorded from 56 unique programs. Program characteristics were obtained from the Scientific Registry of Transplant Recipients. Respondents were transplant surgeons (71%), transplant nephrologists (17%), trainees (9%), and allied professionals (3%). Programs were defined according to annual volume as: low (<5 PT/year), intermediate (6-20), or high (>20). High-volume programs reported that these factors were most important for increased PT: expansion of recipient selection, more aggressive donor utilization, and hiring of PT program-specific personnel. At both the program and national level, the vast majority (82% and 79%, respectively) felt the number of PTs currently performed are not in balance with patients' needs. CONCLUSIONS: Overall, programs reported that the option of PT is not offered adequately to diabetic patients and that strategies to maintain higher PT volume are most evident at intermediate, and especially, high-volume programs.

Assessment and selection of the recipient cows' corpus luteum at the time of embryo transfer, and its influence on conception rate.

OBJECTIVES: To describe the influence of physical traits of the corpus luteum (CL), as described by transrectal ultrasonography on day 6 post-oestrus, on the conception rate following embryo transfer (ET) in recipient beef cows. To investigate if higher recipient utilisation rates were achievable, without compromising conception rates to ET. DESIGN/RESULTS: Data were analysed from Holstein Friesian embryos (n = 1075) frozen in ethylene glycol thawed for direct transfer into one herd of Angus recipient cows. For pregnancies achieved in the program (n = 693), no statistically significant effect was found for the physical traits of the recipients' CL on conception rate (CL volume (P = 0.20), CL side (P = 0.14). Conception rates were similar for recipients with a central lacuna (62%, n = 245) and recipients with no central lacuna (66%, n = 448) (P = 0.10). Of the pregnant recipients with a central lacuna (n = 245), 98.3% had no remaining luteal cavity by the 30-day pregnancy ultrasound. No effect on conception rate was found with either the small (<50% of CL diameter) or large (>50% of CL diameter) central lacunae (P = 0.18). For recipients with CLs that did not meet previous industry selection guidelines (n = 172, 16% of study population), the conception rate (63%) was not significantly different to the routinely selected recipient CLs (n = 903, conception rate 65%) (P = 0.83). CONCLUSIONS: The suitability of a potential ET recipient is determined by observing an appropriately timed oestrus and a detectable CL, regardless of size or quality.

Immunological selection and monitoring of patients undergoing pig kidney transplantation.

Pig kidney xenotransplantation has the potential to alleviate the current shortage of deceased and living human organs and provide patients with end-stage renal disease with a greater opportunity for long-term survival and a better quality of life. In recent decades, advances in the genetic engineering of pigs and in immunosuppressive therapy have permitted the resolution of many historical obstacles to the success of pig kidney transplantation in nonhuman primates. Pig kidney xenotransplantation may soon be translated to the clinic. Given the potential risks of kidney xenotransplantation, particularly of immunologic rejection of the graft, potential patients must be carefully screened for inclusion in the initial clinical trials and immunologically monitored diligently post-transplantation. We provide an overview of the immunological methods we believe should be used to (i) screen potential patients for the first clinical trials to exclude those with a higher risk of rejection, and (ii) monitor patients with a pig kidney graft to determine their immunological response to the graft.