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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Background
Coronavirus disease 2019 (COVID-19) social distancing measures led to a dramatic decline in non-COVID-19 respiratory virus infections, providing a unique opportunity to study their impact ...on annual forced expiratory volume in 1 s (FEV
1
) decline, episodes of temporary drop in lung function (TDLF) suggestive of infection and chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs).
Methods
All FEV
1
values of LTRs transplanted between 2009 and April 2020 at the University Medical Center Groningen (Groningen, The Netherlands) were included. Annual FEV
1
change was estimated with separate estimates for pre-social distancing (2009–2020) and the year with social distancing measures (2020–2021). Patients were grouped by individual TDLF frequency (frequent/infrequent). Respiratory virus circulation was derived from weekly hospital-wide respiratory virus infection rates. Effect modification by TDLF frequency and respiratory virus circulation was assessed. CLAD and TDLF rates were analysed over time.
Results
479 LTRs (12 775 FEV
1
values) were included. Pre-social distancing annual change in FEV
1
was −114 (95% CI −133– −94) mL, while during social distancing FEV
1
did not decline: 5 (95% CI −38–48) mL (difference pre-social distancing
versus
during social distancing: p<0.001). The frequent TDLF subgroup showed faster annual FEV
1
decline compared with the infrequent TDLF subgroup (−150 (95% CI −181– −120)
versus
−90 (95% CI −115– −65) mL; p=0.003). During social distancing, we found significantly lower odds for any TDLF (OR 0.53, 95% CI 0.33–0.85; p=0.008) and severe TDLF (OR 0.34, 0.16–0.71; p=0.005) as well as lower CLAD incidence (OR 0.53, 95% CI 0.27–1.02; p=0.060). Effect modification by respiratory virus circulation indicated a significant association between TDLF/CLAD and respiratory viruses.
Conclusions
During COVID-19 social distancing the strong reduction in respiratory virus circulation coincided with markedly less FEV
1
decline, fewer episodes of TDLF and possibly less CLAD. Effect modification by respiratory virus circulation suggests an important role for respiratory viruses in lung function decline in LTRs.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Monitoring of immunosuppressive drugs such as everolimus and sirolimus is important in allograft rejection prevention in transplant patients. Dried blood spots (DBS) sampling gives ...patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail. Methods A total of 39 sirolimus and 44 everolimus paired fingerprick DBS and whole blood (WB) samples were obtained from 60 adult transplant patients for method comparison using Passing-Bablok regression. Bias was assessed using Bland-Altman. Two validation limits were pre-defined: limits of analytical acceptance were set at >67% of all paired samples within 20% of the mean of both samples and limits of clinical relevance were set in a multidisciplinary team at >80% of all paired samples within 15% of the mean of both samples. Results For both sirolimus and everolimus, Passing-Bablok regression showed no differences between WB and DBS with slopes of 0.86 (95% CI slope, 0.72-1.02) and 0.96 (95% CI 0.84-1.06), respectively. Only everolimus showed a significant constant bias of 4%. For both sirolimus and everolimus, limits of analytical acceptance were met (76.9% and 81.8%, respectively), but limits or clinical relevance were not met (77.3% and 61.5%, respectively). Conclusions Because pre-defined limits of clinical relevance were not met, this DBS sampling method for sirolimus and everolimus cannot replace WB sampling in our center at this time. However, if the clinical setting is compatible with less strict limits for clinical relevance, this DBS method is suitable for clinical application.
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