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We evaluated the outcome of vertical rectus abdominus myocutaneous flap (VRAM) allotransplantation in a mini-pig model, using a combined co-stimulation blockade (Co-SB) and mechanistic target of rapamycin inhibition (mTORi)-based regimen, with or without preceding calcineurin inhibition (CNI).VRAM allotransplants were performed between SLA-mismatched MGH miniature swine. Group A (n = 2) was treated continuously with the mTOR inhibitor rapamycin from day -1 in combination with the Co-SB agent cytotoxic T lymphocyte antigen 4-Ig (CTLA4-Ig) from post-operative day (POD) 0. In group B (n = 3), animals received tacrolimus daily from POD 0 to POD 13, followed by rapamycin daily from POD 7 and CTLA4-Ig weekly from POD 7-28. Graft rejection was determined by Banff criteria and host cellular and humoral immunity monitored.In group A, allografts developed grade-I acute rejection by POD 2 and POD 7, and reached grade-IV by POD 17 and POD 20, respectively. By contrast, in group B, two allografts demonstrated grade-I rejection on POD 30 and grade-IV on POD 74, while the third exhibited grade-I rejection starting on POD 50, though this animal had to be euthanized on POD 58 due to Pneumocystis jirovecii infection. Time-to-event incidence of grade-I rejection was significantly lower in group A compared to group B. During the first 3 weeks post-transplant, no significant differences in anti-donor immunity were observed between the groups.A short course of CNI, followed by combined Co-SB and mTORi significantly delays acute rejection of VRAM allografts in SLA-mismatched miniature swine.

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.

Introduction: Weight gain is a risk factor for poor clinical outcomes following kidney transplantation. Research Question: This study’s aim was a first testing of 2 models to identify patients early after kidney transplantation who are at risk for weight gain and increase in adipose tissue mass in the first year after kidney transplantation. Design: The literature-based models were evaluated on longitudinal data of 88, respectively 79 kidney transplant recipients via ordinary and Firth regression, using gains ≥ 5% in weight and adipose tissue mass respectively as primary and secondary endpoints. Results: The models included physical activity, smoking cessation at time of kidney transplantation, self-reported health status, depressive symptomatology, gender, age, education, baseline body mass index and baseline trunk fat as predictors. Area under the curve was 0.797 (95%-CI 0.702 to 0.893) for the weight model and 0.767 (95%-CI 0.656 to 0.878) for the adipose tissue mass model—showing good, respectively fair discriminative ability. For weight gain ≥ 5%, main risk factors were smoking cessation at time of transplantation (OR 16.425, 95%-CI 1.737-155.288) and better self-reported baseline health state (OR 1.068 for each 1-unit increase, 95%-CI 1.012-1.128). For the adipose tissue mass gain ≥ 5%, main risk factor was overweight/obesity (BMI ≥ 25) at baseline (odds ratio 7.659, 95%-CI 1.789-32.789). Conclusions: The models have potential to assess patients' risk for weight or adipose tissue mass gain during the year after transplantation, but further testing is needed before implementation in clinical practice.

Rather little is known about how psychosocial evaluations for living kidney donation (LKD) are performed. We aimed to explore whether Swiss transplant centers (STCs) vary regarding the rate of living kidney donors refused for psychosocial reasons, the psychosocial evaluation process, and the characteristics of the donors.We investigated 310 consecutive candidates for LKD in 4 of 6 existing STC during mandatory psychosocial evaluations. We registered (i) sociodemographic data, (ii) the type of the decision-making process regarding LKD (ie, snap decision, postponed, deliberate, other), (iii) the evaluator's perception of the donor's emotional bonding and his/her conflicts with the recipient, (iv) the donor's prognosis from a psychosocial perspective, (v) time taken for the psychosocial evaluation, and (vi) its result (eligible, eligible with additional requirements, not eligible).Centers had comparable proportions of noneligible donors (2.9%-6.0%) but differed significantly in the percentage of donors accepted with additional requirements (3.4%-66%,Our results emphasize that it is more important to establish clear guidelines to identify potential psychosocial risks than to stringently standardize the procedure for psychosocial evaluation of living kidney donors.

Introduction: We report on characteristics and lung function outcomes among lung transplant recipients (LTRs) after COVID-19 with infections occurring in the first year of the coronavirus pandemic prior to introduction of the vaccines. Methods: This was a retrospective study of 18 LTRs who tested positive for SARS-CoV-2 between 1 February 2020 and 1 March 2021. The mean age was 49.9 (22–68) years; 12 patients (67%) were male. Two patients died due to severe COVID-19. Results: During the study period, there were 18 lung transplant recipients with a community-acquired SARS-CoV-2 infection. In this cohort, seven had mild, nine had moderate, and two had severe COVID-19. All patients with mild and moderate COVID-19 survived, but the two patients with severe COVID-19 died in the intensive care unit while intubated and on mechanical ventilation. Most patients with moderate COVID-19 showed a permanent lung function decrease that did not improve after 12 months. Conclusion: A majority of LTRs in the current cohort did not experience an alteration in the trajectory of FEV1 evolution after developing SARS-CoV-2 infection. However, in the patients with moderate COVID-19, most patients had a decline in the FEV1 that was present after 1 month after recovery and did not improve or even deteriorated further after 12 months. In LTRs, COVID-19 can have long-lasting effects on pulmonary function. Treatment strategies that influence this trajectory are needed.

BACKGROUND ABO-incompatible (ABOi) kidney transplantation (KT) expands the kidney donor pool and may help to overcome organ shortage. Nonetheless, concerns about infectious complications associated with ABOi-KT have been raised. METHODS In a nationwide cohort (Swiss Transplant Cohort Study), we compared the risk for infectious complications among ABOi and ABO-compatible (ABOc) renal transplant recipients. Infections needed to fulfill rigorous, prespecified criteria to be classified as clinically relevant. Unadjusted and adjusted competing risk regression models were used to compare the time to the first clinically relevant infection among ABOi-KT and ABOc-KT recipients. Inverse probability weighted generalized mixed-effects Poisson regression was used to estimate incidence rate ratios for infection. RESULTS We included 757 living-donor KT recipients (639 ABOc; 118 ABOi) and identified 717 infection episodes. The spectrum of causative pathogens and the anatomical sites affected by infections were similar between ABOi-KT and ABOc-KT recipients. There was no significant difference in time to first posttransplant infection between ABOi-KT and ABOc-KT recipients (subhazard ratio, 1.24; 95% confidence interval [CI], 0.93-1.66; P = 0.142). At 1 y, the crude infection rate was 1.11 (95% CI, 0.93-1.33) episodes per patient-year for ABOi patients and 0.94 (95% CI, 0.86-1.01) for ABOc-KT recipients. Inverse probability weighted infection rates were similar between groups (adjusted incidence rate ratio, 1.12; 95% CI, 0.83-1.52; P = 0.461). CONCLUSIONS The burden of infections during the first year posttransplant was high but not relevantly different in ABOi-KT and ABOc-KT recipients. Our results highlight that concerns regarding infectious complications should not affect the implementation of ABOi-KT programs.

Livers for transplantation from donation after circulatory death donors are relatively more prone to early and ongoing alterations in graft function that might ultimately lead to graft loss and even patient death. In consideration of this fact, this working group of the International Liver Transplantation Society has performed a critical evaluation of the medical literature to create a set of statements regarding the assessment of early allograft function/dysfunction and complications arising in the setting of donation after circulatory death liver transplantation.

Background aims Cultured patient-specific keratinocyte sheets have been used clinically since the 1970s for the treatment of large severe burns. However, despite significant developments in recent years, successful and sustainable treatment is still a challenge. Reliable, high-quality grafts with faster availability and a flexible time window for transplantation are required to improve clinical outcomes. Methods Keratinocytes are usually grown in vitro at 37°C. Given the large temperature differences in native skin tissue, the aim of the authors’ study was to investigate thermal conditioning of keratinocyte sheet production. Therefore, the influence of 31°C, 33°C and 37°C on cell expansion and differentiation in terms of proliferation and sheet formation efficacy was investigated. In addition, the thermal effect on the biological status and thus the quality of the graft was assessed on the basis of the release of wound healing-related biofactors in various stages of graft development. Results The authors demonstrated that temperature is a decisive factor in the production of human keratinocyte sheets. By using specific temperature ranges, the authors have succeeded in optimizing the individual manufacturing steps. During the cell expansion phase, cultivation at 37°C was most effective. After 6 days of culture at 37°C, three times and six times higher numbers of viable cells were obtained compared with 33°C and 31°C. During the cell differentiation and sheet formation phase, however, the cells benefited from a mildly hypothermic temperature of 33°C. Keratinocytes showed increased differentiation potential and formed better epidermal structures, which led to faster biomechanical sheet stability at day 18. In addition, a cultivation temperature of 33°C resulted in a longer lasting and higher secretion of the investigated immunomodulatory, anti-inflammatory, angiogenic and pro-inflammatory biofactors. Conclusions These results show that by using specific temperature ranges, it is possible to accelerate the large-scale production of cultivated keratinocyte sheets while at the same time improving quality. Cultivated keratinocyte sheets are available as early as 18 days post-biopsy and at any time for 7 days thereafter, which increases the flexibility of the process for surgeons and patients alike. These findings will help to provide better clinical outcomes, with an increased take rate in severe burn patients.

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.

Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients.This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26.One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented.This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated.

Kidney transplant recipients (KTRs) with ultralong-term survival represent a growing, yet insufficiently studied patient cohort. In this single-center retrospective study, we analyzed 248 ultralong-term survivors (≥20 years). KTRs were classified into those with superior graft function (defined as eGFR ≥45 ml/min + proteinuria ≤300 mg/day + eGFR-slope ≤ 2 ml/min/1.73 m2/year) and inferior graft function regarding the risk of CKD progression. 20 years post-transplant, median eGFR was 54 ml/min (11–114), proteinuria 200 mg/24 h (0–7,620), eGFR decline 0.45 ml/min/1.73 m2/year (11.7 6.5) and DSA had been detected in 19.7% of KTRs. We identified 96 KTRs (38.7%) with superior (group 1) and 152 KTRs (61.3%) with inferior graft function (group 2). Donation after cardiac death, female sex, glomerulonephritis as primary disease, and early TCMR were independently associated with inferior graft function. Graft survival was significantly better in group 1 compared to group 2 (LogRank, p < 0.001). Besides group affiliation (HR 20.515, p = 0.003), multivariable analysis identified DSA development (HR 3.081, p = 0.023) and donor age (HR 1.032, p = 0.024) as independent factors. Interestingly, there was no significant difference in patient survival (LogRank, p = 0.350). In ultralong-term survivors, excellent graft function refers to superior graft survival but does not extend ultimate patient survival. DSA-formation should be taken seriously even in the ultralong-term.

Approval of the vasopressin V2 receptor antagonist tolvaptan-based on the landmark TEMPO 3:4 trial-marked a transformation in the management of autosomal dominant polycystic kidney disease (ADPKD). This development has advanced patient care in ADPKD from general measures to prevent progression of chronic kidney disease to targeting disease-specific mechanisms. However, considering the long-term nature of this treatment, as well as potential side effects, evidence-based approaches to initiate treatment only in patients with rapidly progressing disease are crucial. In 2016, the position statement issued by the European Renal Association (ERA) was the first society-based recommendation on the use of tolvaptan and has served as a widely used decision-making tool for nephrologists. Since then, considerable practical experience regarding the use of tolvaptan in ADPKD has accumulated. More importantly, additional data from REPRISE, a second randomized clinical trial (RCT) examining the use of tolvaptan in later-stage disease, have added important evidence to the field, as have post hoc studies of these RCTs. To incorporate this new knowledge, we provide an updated algorithm to guide patient selection for treatment with tolvaptan and add practical advice for its use. ispartof: NEPHROLOGY DIALYSIS TRANSPLANTATION vol:37 issue:5 pages:825-839 ispartof: location:England status: published

Background Vaccines against SARS-CoV-2 have been rapidly approved. While pivotal studies were conducted in healthy volunteers, little information is available on safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantations (allo-HCT). Objectives Here, we used a novel assay to analyze patient- and transplant-related factors and their influence on immune responses over an extended period of time (up to 6 months) to the SARS-CoV-2 vaccination in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. Study Design We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) or mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivities against SARS-CoV-2 antigens (receptor-binding domain (RBD), spike glycoprotein subunits S1 and S2, and nucleocapsid protein (N)) was performed prior to vaccination, prior to the 2nd dose, and 1, 3, and 6 months (m) after the 2nd dose. Patients were stratified to three groups (A) 3-6m post HCT; (B) 6-12m post HCT; and (C) >12m post HCT. Results Individuals early post allo-HCT (3-6 and 6-12m post HCT) developed significantly lower antibody titers after vaccination compared to patients >12m post allo-HCT and healthy controls (p65 years (p=0.030), those under immunosuppression for prevention or treatment of graft-vs-host disease (GVHD) (p=0.033), and/or with relapsed disease (p=0.014) displayed poor humoral immune response to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels 1m after the 2nd dose of the vaccine but substantially waned in all transplanted groups and healthy controls over time. Conclusions This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding re-vaccination and social behavior during the SARS-CoV-2 pandemic., Graphical Abstract Image, graphical abstract

The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

Outbreaks of viral infections, such as measles, are regularly observed and pose a serious threat to recipients of allogeneic hematopoietic cell transplantation (HCT). The questions of how long cellular and humoral protective host immunity persists, and whether donor immunity can be transferred has not been clarified. Here we present a retrospective analysis of humoral immunity—serial antibody titers against measles, mumps, and rubella—in 331 patients who underwent allogeneic HCT at our single center between 2002 and 2015. Associations between the loss of protective antibody levels and clinical patient characteristics and transplantation parameters were examined. In general, antibody protection against measles persisted longer, with 72% of patients maintaining sufficient titers at 5 years post-HCT even without revaccination, while at that time only 65% and 50% of patients had protective immunity against rubella and mumps, respectively. The great majority of donors were seropositive for all 3 viruses; however, it appeared that donor humoral immunity could not be transferred and had no impact on post-HCT serostatus. Rather, the most relevant factor for persistent protective antibody titers against measles and rubella was whether patients were born before the introduction of the respective vaccine and thus were immunized by the wild-type disease-inducing virus instead of the vaccine. Moreover, the presence of moderate and severe chronic graft-versus-host disease (GVHD) was associated with more rapid loss of immune protection. In contrast, underlying disease, intensity of the conditioning regimen, use of antithymocyte globulin, age, and graft source had no influence on antibody titers. Overall, our findings suggest that the majority of antibodies against measles, mumps, and rubella originate from residual host cells, whereas donor immune status appears to have no influence on antibody protection post-HCT.

Nutrition intervention is an essential component of kidney disease management. This study aimed to understand current global availability and capacity of kidney nutrition care services, interdisciplinary communication, and availability of oral nutrition supplements.The International Society of Renal Nutrition and Metabolism (ISRNM), working in partnership with the International Society of Nephrology (ISN) Global Kidney Health Atlas Committee, developed this Global Kidney Nutrition Care Atlas. An electronic survey was administered among key kidney care stakeholders through 182 ISN-affiliated countries between July and September 2018.Overall, 160 of 182 countries (88%) responded, of which 155 countries (97%) answered the survey items related to kidney nutrition care. Only 48% of the 155 countries have dietitians/renal dietitians to provide this specialized service. Dietary counseling, provided by a person trained in nutrition, was generally not available in 65% of low-/lower middle-income countries and "never" available in 23% of low-income countries. Forty-one percent of the countries did not provide formal assessment of nutrition status for kidney nutrition care. The availability of oral nutrition supplements varied globally and, mostly, were not freely available in low-/lower middle-income countries for both inpatient and outpatient settings. Dietitians and nephrologists only communicated "sometimes" on kidney nutrition care in ≥60% of countries globally.This survey reveals significant gaps in global kidney nutrition care service capacity, availability, cost coverage, and deficiencies in interdisciplinary communication on kidney nutrition care delivery, especially in lower-income countries.

The potential for a donor-derived transmission of porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) to the recipient has been recognized since pigs were considered candidate donors for xenotransplantation. This review gives a short description of the viral properties and summarizes the current evidence of the effects of PCMV/PRV transmission in preclinical xenotransplantation. Despite evidence that PCMV/PRV does not infect human and non-human primate cells, activation in the transplanted organ and detrimental systemic complications have been described. As PCMV/PRV is a herpesvirus able to establish latency, the importance of adequate screening of donor pigs is emphasized, as no efficient treatment is available. Furthermore, easy and successful ways of elimination of PCMV/PRV from pig herds are indicated.

Longitudinal data on pulmonary function after pediatric allogeneic or autologous hematopoietic stem cell transplantation (HSCT) are rare. We examined pulmonary function and associated risk factors in 5-year childhood cancer survivors (CCSs) longitudinally. We included 74 CCSs diagnosed between 1976 and 2010, treated with HSCT, and with at least two pulmonary function tests performed during follow-up. Median follow-up was 9 years (range 6–13). We described pulmonary function as z-scores for lung volumes (forced vital capacity [FVC], residual volume [RV], total lung capacity [TLC]), flows (forced expiratory volume in 1 s [FEV1], maximal mid-expiratory flow [MMEF]), and diffusion capacity for carbon monoxide (DLCO) and assessed associations with potential risk factors using multivariable regression analysis. The median z-scores for FEV1, FVC, and TLC were below the expected throughout the follow-up period. This was not the case for RV, MMEF and DLCO. Female gender, radiotherapy to the chest, and relapse were associated with lower z-scores of FEV1, FVC, MMEF, RV or DLCO. Childhood cancer survivors after HSCT are at risk of pulmonary dysfunction. The complex and multifactorial etiology of pulmonary dysfunction emphasizes the need for longitudinal prospective studies to better characterize the course and causes of pulmonary function impairment in CCSs.

We aimed to identify, assess, compare and map research priorities of patients and professionals in the Swiss Transplant Cohort Study. The project followed 3 steps. 1) Focus group interviews identified patients’ (n = 22) research priorities. 2) A nationwide survey assessed and compared the priorities in 292 patients and 175 professionals. 3) Priorities were mapped to the 4 levels of Bronfenbrenner’s ecological framework. The 13 research priorities (financial pressure, medication taking, continuity of care, emotional well-being, return to work, trustful relationships, person-centredness, organization of care, exercise and physical fitness, graft functioning, pregnancy, peer contact and public knowledge of transplantation), addressed all framework levels: patient (n = 7), micro (n = 3), meso (n = 2), and macro (n = 1). Comparing each group’s top 10 priorities revealed that continuity of care received highest importance rating from both (92.2% patients, 92.5% professionals), with 3 more agreements between the groups. Otherwise, perspectives were more diverse than congruent: Patients emphasized patient level priorities (emotional well-being, graft functioning, return to work), professionals those on the meso level (continuity of care, organization of care). Patients’ research priorities highlighted a need to expand research to the micro, meso and macro level. Discrepancies should be recognized to avoid understudying topics that are more important to professionals than to patients.

Background As a result of the COVID-19 widespread pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. Objectives To compare the outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). Study design We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 as compared to 60 consecutive patients who received fresh allografts prior to the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment, graft failure (GF) and secondary outcomes were overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved versus prospectively collected fresh apheresis samples. Results Compared to fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced intensity conditioning (RIC) allo-HCT with median times to engraftment of 24 days vs 18 days (P = .01) and 27 days vs 18 days (P = .069), respectively. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) vs only one of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid and T-cell donor chimerism at 1 month. OS and RFS were inferior for cryograft recipients with hazard ratio [HR (95%Cl)]: 2.16 (1.00, 4.67) and 1.90 (0.95, 3.79), respectively. Using an extended immunophenotype analysis we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both decrease in total cell viability and significantly reduced absolute numbers of NK cells (CD3−CD56+) in the cryopreserved apheresis samples. Conclusion In this single institution study we note delayed engraftment and a trend toward clinical inferiority of cryopreserved vs fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

Food-safety measures are recommended to solid organ transplant (SOT) recipients. However, the burden of foodborne infections in SOT recipients has not been established. We describe the epidemiology and outcomes of bacterial foodborne infections in a nationwide cohort including 4405 SOT recipients in Switzerland between 2008 and 2018. Participants were prospectively followed for a median of 4.2 years with systematic collection of data on infections, and patient and graft-related outcomes. We identified 151 episodes of microbiologically confirmed bacterial foodborne infections occurring in median 1.6 years (IQR 0.58-3.40) after transplantation (131 [88%] Campylobacter spp. and 15 [10%] non-typhoidal Salmonella). The cumulative incidence of bacterial foodborne infections was 4% (95% CI 3.4-4.8). Standardized incidence rates were 7.4 (95% CI 6.2-8.7) and 4.6 (95% CI 2.6-7.5) for Campylobacter and Salmonella infections, respectively. Invasive infection was more common with Salmonella (33.3% [5/15]) compared to Campylobacter (3.2% [4/125]; p = .001). Hospital and ICU admission rates were 47.7% (69/145) and 4.1% (6/145), respectively. A composite endpoint of acute rejection, graft loss, or death occurred within 30 days in 3.3% (5/151) of cases. In conclusion, in our cohort bacterial foodborne infections were late post-transplant infections and were associated with significant morbidity, supporting the need for implementation of food-safety recommendations.

Background: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. Method: This is a retrospective national database analysis of children

BACKGROUND Since lung transplantation became a viable option for cystic fibrosis (CF) lung disease, adult transplant recipients with CF have superior survival than all the other major diagnostic indications. However, among adults, recipients with CF have a younger age at transplant than other transplant recipients. Over time, the frequency and proportion of lung transplants for CF has increased for adults compared with children. Using a large international transplant registry, we investigated time trends in numbers of transplants, age at transplant, and post-transplant survival and cause of death for recipients with CF. METHODS We conducted a retrospective cohort study of primary lung-alone deceased-donor transplants with a primary diagnostic indication of CF reported to the International Society for Heart and Lung Transplantation Thoracic Transplant Registry from January 2005 through December 2014. We assessed outcomes through December 31, 2015. The study defined the pediatric group as age

Background: Autologous stem cell transplantation is considered a standard of care treatment in eligible patients with multiple myeloma, but puts the patient at high risk for infections and bleeding complications. Acquired von-Willebrand's disease (AVWD) and acquired platelet dysfunction are rare bleeding disorders that are associated with lymphoproliferative disorders such as multiple myeloma. Patients with acquired bleeding disorders who are planned for ASCT to treat the underlying condition are considered at highest risk for bleeding complications, and optimal treatment strategies are not known. Materials and Methods: We summarized the diagnostic and therapeutic approach to a patient affected by AVWD and acquired platelet disorder related to multiple myeloma. The patient who was planned for ASCT presented with moderate to severe bleeding symptoms. Results: Acute bleeding episodes were successfully controlled and prevented during induction and consolidation therapy with immunoglobulins, whereas replacement of plasma-derived VW factor showed no clinical improvement. High-dose melphalan-based consolidation therapy supported with autologous stem-cell transplantation led to an immediate and sustainable rise of von-Willebrand antigen and activity and a subsequent normalization of platelet aggregation activity. After a follow-up of 40 weeks, the patient maintained normalized VW levels and platelet aggregation capacity. There were no further signs or symptoms of bleeding. Conclusion: This case report highlights the necessity for combined supportive and causal treatment in patients with AVWD and paraproteinemic PD. High-dose melphalan with autologous stem cell support may function as a treatment option in patients with myeloma-related AVWD.

BACKGROUND Little is known regarding the optimal management of nocardiosis among solid organ transplant (SOT) recipients. It is often suggested to avoid trimethoprim/sulfamethoxazole (TMP-SMX) monotherapy in heavily immunocompromised patients (such as SOT recipients) and/or in case of severe or disseminated nocardiosis. Our aim was to report our experience with TMP-SMX monotherapy in SOT recipients with nocardiosis. METHODS Using data from a previously published European study, we assessed the incidence of adverse events in SOT recipients receiving TMP-SMX monotherapy and assessed its effectiveness. RESULTS Thirty-one SOT recipients with nocardiosis were included, mostly kidney transplant recipients (20/31, 65%). Eleven (36%) had disseminated infection, and four (13%) had brain nocardiosis. Most patients had lung and/or pleural involvement (26/31, 84%). Daily dose of trimethoprim at initiation was 10 [6.4-14.8]��mg/kg. The median estimated glomerular filtration rate at time of diagnosis of nocardiosis was 44 [30-62] ml/min/1.73��m��. TMP-SMX was discontinued prematurely in one third of the patients (10/31, 32%, mostly for hematological toxicity [n��=��3] or increased serum creatinine [n��=��3]). Focusing on the 24 (77%) patients who completed at least 30��days of TMP-SMX monotherapy, 4 had late (>30��days) drug discontinuation, 1 experienced treatment failure, and 19 completed planned TMP-SMX monotherapy. Clinical outcome was favorable in these 19 patients, despite the fact that 8 (42%) had disseminated infection and 2 (11%) brain nocardiosis. Overall, all-cause 1-year mortality was 10% (3/31). CONCLUSIONS TMP-SMX monotherapy appears to be effective for the treatment of most nocardiosis among SOT recipients. Interventional studies are needed to compare its safety and effectiveness with those of other regimens used to treat posttransplant nocardiosis.

Chronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled-DCD lungs are an effective and safe method with good mid-term and even long-term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled-DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled-DCD-lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long-term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex-vivo lung perfusion is promising.

Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60-70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow-up was 4.7 years. Failure-free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure-free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5-year failure-free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post-transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure-free outcome, with sustained quality of life.

Background RGT is a major cause for early graft loss after KTx. Although evidence-based recommendations are lacking, aP is often used to prevent RGT. This systematic review aimed to determine the effectiveness and safety of aP in adult and pediatric KTx recipients. Methods MEDLINE, EMBASE, Cochrane Controlled Trials Register, conference proceedings, and electronic databases for trial registries were searched for eligible studies using search terms relevant to this review (April 21, 2020). The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Results Twelve studies comprising 2370 patients (adult = 1415, pediatric = 955) were included, of which three were RCTs. The overall risk for developing RGT was lower in the group with aP compared with the control group (RR 0.24, 95% confidence interval 0.12-0.49). The antithrombotic drugs used were heparin (7/12), acetylsalicylic acid (2/12), a combination of both (2/12), and dipyridamole (1/12) with a high variability in timing, dosing, and mode of application. Adverse effects were reported rarely, with minor bleeding as the main complication. The non-randomized studies had significant risks of bias in the domains of patient selection, confounder, and measurement of outcomes. Conclusion Based on pooled analysis, aP seems to reduce the risk of RGT in KTx. However, the reliability of these results is limited, as the quality of the available studies is poor and information on adverse effects associated with aP is scarce. Additional high-quality research is urgently needed to provide sufficient data supporting the use of aP in KTx.

Reduced immunosuppression during BKV-DNAemia has been associated with T-cell mediated rejection (TCMR), de novo donor-specific antibodies (DSA) and antibody-mediated rejection (ABMR). Intravenous immunoglobulins (IVIG) may reduce alloimmunity. We studied 860 kidney transplant recipients (KTRs) for the development of BKV-DNAuria and BKV-DNAemia (low-level10 000 IE/ml, high-level10 000 IE/ml). 52/131 KTRs with high-level BKV-DNAemia received IVIG. The HLA-related immunological risk was stratified by the Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) algorithm. BKV-DNAuria only was observed in 86 KTRs (10.0%), low-level BKV-DNAemia in 180 KTRs (20.9%) and high-level BKV-DNAemia in 131 KTRs (15.2%). KTRs with low-level BKV-DNAemia showed significantly less TCMR compared to KTRs with high-level BKV-DNAemia (5.2% vs. 25.5%; P 0.001) and no BKV-replication (13.2%; P = 0.014), lowest rates of de novo DSA (21.3%), ABMR (9.2%) and flattest glomerular filtration rate (GFR) slope (-0.8 ml/min). KTRs with low-level BKV-DNAemia showed significantly higher median (interquartile range) total PIRCHE if they developed TCMR [100.22 (72.6) vs. 69.52 (49.97); P = 0.020] or ABMR [128.86 (52.99) vs. 69.52 (49.96); P = 0.005]. Administration of IVIG did not shorten duration of BKV-DNAemia (P = 0.798) or reduce TCMR, de novo DSA and ABMR (P 0.05). KTRs with low-level BKV-DNAemia showed best protection against alloimmunity, with a high number of PIRCHE co-determining the remaining risk. The administration of IVIG, however, was not beneficial in reducing alloimmunity.

In donation after circulatory death (DCD), cardiac grafts are subjected to warm ischemia in situ, prior to a brief period of cold, static storage (CSS) at procurement, and ex situ, normothermic, machine perfusion (NMP) for transport and graft evaluation. Cold ischemia and normothermic reoxygenation during NMP could aggravate graft injury through continued accumulation and oxidation, respectively, of mitochondrial succinate, and the resultant oxidative stress. We hypothesized that replacing CSS with hypothermic, oxygenated perfusion (HOPE) could provide cardioprotection by reducing cardiac succinate levels before NMP. DCD was simulated in male Wistar rats. Following 21 minutes in situ ischemia, explanted hearts underwent 30 minutes hypothermic storage with 1 of the following: (1) CSS, (2) HOPE, (3) hypothermic deoxygenated perfusion (HNPE), or (4) HOPE + AA5 (succinate dehydrogenase inhibitor) followed by normothermic reperfusion to measure cardiac and metabolic recovery. After hypothermic storage, tissue ATP/ADP levels were higher and succinate concentration was lower in HOPE vs CSS, HNPE, and HOPE + AA5 hearts. After 60 minutes reperfusion, cardiac function was increased and cellular injury was decreased in HOPE compared with CSS, HNPE, and HOPE + AA5 hearts. HOPE provides improved cardioprotection via succinate oxidation prior to normothermic reperfusion compared with CSS, and therefore is a promising strategy for preservation of cardiac grafts obtained with DCD.

Background: Chronic lung allograft dysfunction (CLAD) and its obstructive form, the obliterative bronchiolitis (OB), are the main long-term complications related to high mortality rate postlung transplantation. CLAD treatment lacks a significant success in survival. Here, we investigated a new strategy through inhibition of the proinflammatory mitogen- and stress-activated kinase 1 (MSK1) kinase. Methods: MSK1 expression was assessed in a mouse OB model after heterotopic tracheal allotransplantation. Pharmacological inhibition of MSK1 (H89, fasudil, PHA767491) was evaluated in the murine model and in a translational model using human lung primary fibroblasts in proinflammatory conditions. MSK1 expression was graded over time in biopsies from a cohort of CLAD patients. Results: MSK1 mRNA progressively increased during OB (6.4-fold at D21 posttransplantation). Inhibition of MSK1 allowed to counteract the damage to the epithelium (56% restoration for H89), and abolished the recruitment of MHCII+ (94%) and T cells (100%) at the early inflammatory phase of OB. In addition, it markedly decreased the late fibroproliferative obstruction in allografts (48%). MSK1 inhibitors decreased production of IL-6 (whose transcription is under the control of MSK1) released from human lung fibroblasts (96%). Finally, we confirmed occurrence of a 2.9-fold increased MSK1 mRNA expression in lung biopsies in patients at 6 months before CLAD diagnosis as compared to recipients with stable lung function. Conclusions: These findings suggest the overall interest of the MSK1 kinase either as a marker or as a potential therapeutic target in lung dysfunction posttransplantation.