Sufficient physical activity is important for solid organ transplant recipients (heart, lung, liver, kidney). However, recipients do not meet the recommended amount or required type of physical ...activity. The perceived barriers to and facilitators of physical activity in this population are largely unknown.
Semi-structured in depth interviews were conducted with solid organ transplant recipients in order to explore experienced barriers and facilitators. Qualitative methodology with thematic line-by-line analysis was used for analysis, and derived themes were classified into personal and environmental factors.
The most important indicated barriers were physical limitations, insufficient energy level, fear, and comorbidities. The most frequently mentioned facilitators included motivation, coping, consequences of (in)activity, routine/habit, goals/goal priority, and responsibility for the transplanted organ. Neutral factors acting as a barrier or facilitator were self-efficacy and expertise of personnel. A comparison of barriers and facilitators between transplant recipient groups yielded no overt differences.
Several personal and environmental factors were indicated that should be considered in intervention development to increase physical activity behavior in solid organ transplant recipients.
The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as ...a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers.
Short-term survival after solid-organ transplantation has substantially improved, and the focus has shifted to long-term survival, including the role of physical activity (PA). Knowledge about PA and ...sedentary time in recipients of solid-organ transplantation is limited, and identification of the levels and associated factors is necessary for intervention development.
The objectives of this study were to investigate the level of PA and sedentary time in recipients of solid-organ transplantation and to identify factors associated with these behaviors.
The design consisted of a cross-sectional survey.
Questionnaires on PA level, sedentary time, and potential associated factors were used for recipients of solid-organ transplantation (kidney, liver, lung, and heart N = 656). Multiple regression analyses with a variable selection procedure were used.
Fewer than 60% of the recipients fulfilled the PA guideline. Factors significantly associated with a lower level of PA included being a woman, younger age (nonlinear), not actively working or being retired, physical limitations, and low expectations and self-confidence. Factors significantly associated with less sedentary time included exercise self-efficacy and not actively working or being retired. Significantly associated with more sedentary time were a high education level, fear of negative effects, physical limitations, and the motivator "health and physical outcomes." The type of transplantation did not significantly influence either of the outcome measures.
The design did not allow for causal inferences to be made. The studied associated factors were limited to individual and interpersonal factors. Self-reported measures of PA and sedentary time were used.
In intervention development directed at increasing the level of PA and reducing sedentary time in recipients of solid-organ transplantation, attention should be paid to physical limitations, fear of negative effects, low expectations and self-confidence, health and physical outcomes, and exercise self-efficacy.
Organ transplantation is a lifesaving option for patients with advanced diseases. Rejection is regarded as one of the most severe risk factors post-transplantation. A molecule that contributes to ...immune tolerance and resisting rejection is human leukocyte antigen (HLA)-G, which belongs to the non-classical major histocompatibility complex class (MHC) I family. HLA-G was originally found to play a role during pregnancy to maintain immune tolerance between mother and child. It is expressed in the placenta and detected in several body fluids as soluble factor as well as different membrane isoforms on cells. Recent findings on HLA-G show that it can also play multifaceted roles during transplantation. This review will explain the general characteristics and biological function of HLA-G and summarize the views supporting the tolerogenic and other roles of HLA-G to better understand its role in solid organ transplantation (SOT) and its complications. Finally, we will discuss potential future research on the role of HLA-G in prevention, diagnosis, and treatment in SOT.
It is generally unknown to what extent organ transplant recipients can be physically challenged. During an expedition to Mount Kilimanjaro, the tolerance for strenuous physical activity and ...high-altitude of organ transplant recipients after various types of transplantation was compared to non-transplanted controls.
Twelve organ transplant recipients were selected to participate (2 heart-, 2 lung-, 2 kidney-, 4 liver-, 1 allogeneic stem cell- and 1 small bowel-transplantation). Controls comprised the members of the medical team and accompanying family members (n = 14). During the climb, cardiopulmonary parameters and symptoms of acute mountain sickness were recorded twice daily. Capillary blood analyses were performed three times during the climb and once following return.
Eleven of the transplant participants and all controls began the final ascent from 4700 meters and reached over 5000 meters. Eight transplant participants (73%) and thirteen controls (93%) reached the summit (5895m). Cardiopulmonary parameters and altitude sickness scores demonstrated no differences between transplant participants and controls. Signs of hyperventilation were more pronounced in transplant participants and adaptation to high-altitude was less effective, which was related to a decreased renal function. This resulted in reduced metabolic compensation.
Overall, tolerance to strenuous physical activity and feasibility of a high-altitude expedition in carefully selected organ transplant recipients is comparable to non-transplanted controls.
Concerns have been raised on the impact of coronavirus disease (COVID-19) on lung transplant (LTx) patients. The aim of this study was to evaluate the transplant function pre- and post-COVID-19 in ...LTx patients.
Data were retrospectively collected from LTx patients with confirmed COVID-19 from all 3 Dutch transplant centers, between February 2020 and September 2021. Spirometry results were collected pre-COVID-19, 3- and 6-months post-infection.
Seventy-four LTx patients were included. Forty-two (57%) patients were admitted, 19 (26%) to the intensive care unit. The in-hospital mortality was 20%. Twelve out of 19 ICU patients died (63%), a further 3 died on general wards. Patients with available spirometry (78% at 3 months, 65% at 6 months) showed a significant decline in mean FEV1 (ΔFEV1 138 ±39 ml, p = 0.001), and FVC (ΔFVC 233 ±74 ml, p = 0.000) 3 months post-infection. Lung function improved slightly from 3 to 6 months after COVID-19 (ΔFEV1 24 ±38 ml; ΔFVC 100 ±46 ml), but remained significantly lower than pre-COVID-19 values (ΔFEV1 86 ml ±36 ml, p = 0.021; ΔFVC 117 ±35 ml, p= 0.012). FEV1/FVC was > 0.70.
In LTx patients COVID-19 results in high mortality in hospitalized patients. Lung function declined 3 months after infection and gradually improved at 6 months, but remained significantly lower compared to pre-COVID-19 values. The more significant decline in FVC than in FEV1 and FEV1/FVC > 70%, suggested a more restrictive pattern.
Acute respiratory distress syndrome (ARDS) is a rapidly progressive lung disease with a high mortality rate. Although lung transplantation (LTx) is a well‐established treatment for a variety of ...chronic pulmonary diseases, LTx for acute lung failure (due to ARDS) remains controversial. We reviewed posttransplant outcome of ARDS patients from three high‐volume European transplant centers. Demographics and clinical data were collected and analyzed. Viral infection was the main reason for ARDS (n = 7/13, 53.8%). All patients were admitted to ICU and required mechanical ventilation, 11/13 were supported with ECMO at the time of listing. They were granted a median LAS of 76 (IQR 50–85) and waited for a median of 3 days (IQR 1.5–14). Postoperatively, median length of mechanical ventilation was 33 days (IQR 17–52.5), median length of ICU and hospital stay were 39 days (IQR 19.5–58.5) and 54 days (IQR 43.5–127). Prolongation of peripheral postoperative ECMO was required in 7/13 (53.8%) patients with a median duration of 2 days (IQR 2–7). 30‐day mortality was 7.7%, 1 and 5‐year survival rates were calculated as 71.6% and 54.2%, respectively. Given the lack of alternative treatment options, the herein presented results support the concept of offering live‐saving LTx to carefully selected ARDS patients.
In the largest cohort study from 3 European high‐volume centers, lung transplantation as a rescue therapy in 13 highly selected patients with acute respiratory distress syndrome bridged on mechanical ventilation or ECMO between August 1998 and May 2020, 30‐day mortality was 7.7% with 1‐year and 5‐year survival rates of 71.6% and 54.2%, respectively.
Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and ...highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.
Purpose
Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to ...define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients.
Methods
An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert.
Results
An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra‐operative antimicrobials); (3) invasive aspergillosis (treatment of culture‐negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis).
Conclusion
This Delphi panel developed consensus‐based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.
This study uses a modified Delphi method to develop consensus‐based recommendations for 10 infectious clinical syndromes commonly encountered in thoracic transplant recipients and mechanical circulatory recipients. Consensus was reached among 62% (36/58) of questions.