Solid Organ Transplantation PDF

Solid Organ Transplantation Kevin Brueilly, PT, PhD Clin Med III; Fall 2024  History of Organ Transplantation Advances in surgical, storage, transport, and immunology/rejection techniques have greatly increased the possibility of the life-changing surgery. O...

Solid Organ Transplantation Kevin Brueilly, PT, PhD Clin Med III; Fall 2024  History of Organ Transplantation Advances in surgical, storage, transport, and immunology/rejection techniques have greatly increased the possibility of the life-changing surgery. Organs for transplantation remain to be the rate limiting factor for transplant procedures.  Organs available for transplantation Heart Lung Liver Pancreas Kidney Bone Marrow Intestine Skin Bone Veins Soft tissue (cartilage) Heart valve Cornea Eye Types of transplantation Allograft- within same Xenogenic (Heterologous)- species (Allogenic) among differing species Autologous- within same Orthotopic- donor tissue to individual normal anatomic site Samespecies to same site Syngenic- between Heterotopic- donor tissue to identical twins other area of body testlilljection  Candidacy for Transplantation Compatibility Blood type Organ type plane Donor age Urgency v.pt ETecwntersisities Medical condition Medical management Importance Prognosis/Comorbidity Geographic availability Body weight Past compliance with treatment (*At least 30% of all steatosis cases can be attribute to alcohol $$$$$$$$ political outside motivation Tissue Engineering and Regenerative Medicine Most technology focuses on skin and connective tissue replacement https://apligraf.com/apligraf-overview/ Autologous cells knee cartilage Build mateinthe Stem cell research ongoing Artificial pancreas in development of more than 20 years Lim et al. Tissue engineering of decellularized pancreas scaffolds for regenerative medicine in diabetes. Acta Biomaterialia. 2023(157):49-66  The medicines of transplantation Purpose: To Prevent and then to Treat ÉES Rejection ___________ Infection Inflammation ___________ 1. Calcineurin inhibitors- Cyclosporine blocks IL-2 (fewer killer T cells) 2. Antimetabolites- CellCept, Cytoxin depresses replication of attacking cells (BM, macroph) 3. Cortocosteroids- Prednisone blocks IL-2 Psychosocial Aspects Consider a patient has a terminal diagnosis unless a donor/intervention can be found. Think about the emotions as you or a loved one wait for life to end so another can continue! Post-transplant guilt is real. A family member/donor gave up their viable organ. Someone had to die for you to live. Are you worthy of such responsibility? Post-transplant Complications 3 categories 1. surgery related 2. transplanted tissue related 3. immunosuppressive agent related Pre-transplant tissue testing To protect recipient from infectious agents such as: CMV VRE Hep B Disqualification Hep C Not aDefinite HIV Ischemic Reperfusion Injury Incidence- 12 to 87% Organ/tissue without blood flow after harvest Ischemic vessel response ensues Post-transplant flow is abrupt and turbulent Inflammatory response with leukocytes and platelets aggregation Effects last 3-5 days Complications Post-transplant Rejection GFHD HostRejecting tissue Implanting Immunosuppression Wound Healing  Tissue Rejection Improved by Histocompatibility- antigen reaction reduced by tissue typing personnel (PhD in Genetic Immun) Hyperacute rejection- immediate 2° coagulation response Elefryers Acute- days to years, antigen related rejection, managed by immunosuppressive drugs Chronic- 3 months to years, related to chronic vascular changes of tissue/organ, managed by immunosuppressive drugs Signs of rejection Asymptomatic Flu-like symptoms Loss of appetite Graft tenderness BP Δs Dyspnea Fatigue Skin lesions Peripheral edema Reduced exercise tolerance Organ specific signs (e.g. pancreas=n/v)  Graft-vs-Host Disease (GVHD) Grafted material T lymphocytes act against the host tissue. Very serious reactions Fever, rash, GI symptoms, neuropathy If untreated- results in death High-dose corticosteroids and immunosuppression are used to treat. Immunosuppression 1. Long-term therapy can cause associated conditions INFECTION Cleanhands Diabetes é Hyperlipidemia CV disease FETES Osteoporosis Steroid induced myopathies Neuropathies Tremor Paresthesia Seizure Demyelinating polyradiculopathy Quadriplegia 2. Cancers due to Immunosuppression Rate 3 X non-recipients Up to 100 X more frequent Appears to be related to amount of immunosuppression (Cardiac = more risk) Skin CA, Karposi sarcoma, & lymphomas lead the list  Transplantation and Exercise Patients generally deconditioned prior to transplantation. Many also unmotivated to exercise 2 psychological effects of condition causing need for transplantation. Often patients are to the point of fragility Weakness, Dyspnea & Fatigue on exertion were day you for every doel laying back 3 to get  Y Goals of pre & post transplant PT Intervention Targeted at required life activities 1. Quality of Life activities Exercise associated with ADL’s (functional mobility), Anti-depression 2. Activities of need Work, Exercise, Anti-depression 3. Activities of leisure  Pre-transplant physical therapy cookbook Not a Dependent Functional activity AND Exercise be pt Mobility will ADL specific Patient specific to improve function, esteem, and self-control Strengthening should focus on proximal musculature Pelvis, Glutes, Quads, Shoulders muscleMovers primary Glucocorticoids causes muscle meekness proximal  Efficacy of pre-t exercise Goal is to offset effects of immobility/deconditioning continuing corticosteroids Studies that examine pre vs. post-t performance are limited and generalizations are difficult due to varied pre-transplant condition and various outcome measures chosen Always need more studies focused on survivability and QOL  Post-t Exercise Considerations A comparison of two patients Bob: 40 y/o, Received a new liver yesterday Ron: 65 y/o, Received a new knee yesterday How are both of these patients similar? How are both of these patients different?  Recognize h Post t-plant exercise Indicators when.to Totellus Exercise is valuable to improve CV, strength, and overall QoL. Attenuates the effect of immunosuppression. When do you think it could begin/progress? Presentation How they Did in Surgery agree Do you think there are any limitations specific to the transplanted organ?  When pancreas failstheywhole Rodney Disenic Kidney, Bladder, Liver, Pancreas (and combinations of all) How do you think these patients would differ in rehab needs following transplant? How would they be the same? - They all are likely to need reconditioning and general strengthening What do we need to watch for in treatment? IncreasedHR SOB Assistance NeedingMore - Certainly general signs of exercise intolerance mightstartestispule - There are sone specifics associated with some of these transplants that we should be watching for… Liver Transplant Procedure  2-12 hour procedure Very skilled surgeon and surgery team Done under general anesthesia Surgical incision (U or Y shaped) Remove present liver Replace with donor liver Reattach all vessels and ducts Close abdominal cavity Just under 12,000 LT cases performed in 2023 in the US 54% of patients on waiting list received a transplant within 12 months (2021) 24,000 transplant candidates on the waiting list 2022 5 year survival rate (2019) for Liver CA Without transplantation – 22% With transplant- 75% HRSA Scientific Registry of Transplant Recipients, 2022  https://www.youtube.com/watch?v=8ufoR2cQ04g of thecan is one Liver refow Living donor procedure (6%) few I Bite(94%) Deceased donor procedure someone Site specific and patient tolerance choices: 12hours ICU LOS forabout Icu Hospital LOS  Liver Rehab Two practice recommendations related to in-patient rehabilitation following LT were yielded from this review: (1) it is safe, tolerable, and feasible; and (2) it improves postoperative functional outcomes (Review >3,900 patients; Santa mina et al; 2022) Prehabilitation prior to liver transplantation is unlikely to be harmful, and likely to have short term benefits on functional status. We cautiously recommend prehabilitation on the basis of absence of harm and possibility of benefit (Review reported 1 study; Vinaixa et al; 2022) Approximately one-half of all patients undergoing LT have varying degrees of myocardial abnormalities before surgery. Advanced liver disease causes persistent splanchnic dilation and systemic hyperdynamic changes, resulting in myocardial remodeling and systolic and diastolic dysfunction. Consider CV risk factors prior to treatment (Lv; 2022) Early rehabilitation in liver transplant patients can significantly reduce complications and length of ICU stay (Lv; 2022) *Compare to Vinaixa conclusions  A personalized rehabilitation protocol should be developed based on the patients' conditions (Lv; 2022) Perioperative rehabilitation has been shown to be safe in patients undergoing heart/lung transplantation and in healthy patients. The perioperative condition of patients who have undergone LT is complex and variable, and safety hazards caused by rehabilitation intervention are a focus of our attention.(Lv; 2022) Rehabilitation exercises should be performed 24 h after surgery. Rehabilitation exercise should be postponed in patients with insufficient oxygen transport, such as those with acute respiratory distress, hemodynamic instability, and severe coagulation disorders, including active bleeding, risk of massive deep vein thrombosis, and extensive poor wound healing. (Lv; 2022) Cochrane Review- Based on very low-certainty evidence in our systematic review, we are very uncertain of the role of exercise training (aerobic, resistance based exercises, or both) in affecting mortality, health-related quality of life, and physical function (i.e. aerobic capacity and muscle strength) in liver transplant recipients. There were few data on the composite of cardiovascular mortality and cardiovascular disease, cardiovascular disease post-transplantation, and adverse event outcomes. We lack larger trials with blinded outcome assessment (Pérez-Amate; 2023) Scores  y y Early resistance training may improve muscle strength, exercise capacity, physical performance, and fatigue perception in liver recipients, when added to standard physiotherapy. The estimated minimal clinically important differences are meaningful to clinicians in setting liver transplanted patient-specific goals (Yüksel Ergene; 2022)  Focus on Red Liver transplant rehab Living Donor Maintenance and improvement of bed mobility, transfers and ambulation Wound care Preparation for discharge to home Recipient skin protection splintingofabodmen effetffs Maintenance and improvement of bed mobility, transfers and ambulation proximal musculature General strengthening as necessary (focus on _________ ____________) Wound care Instruction in HEP Family education Evaluation and preparation for discharge destination Bathing and posture  Kidney Transplant The most common transplant procedure performed in the US In 2022, 26,309 transplanted patients (HRSA; 2022) 44,000 on the waiting list (2022) Living donor Deceased donor 5 year survival rate of patients with Kidney CA Without transplant- 78% With transplant- 78% (deceased donor) and 88% (living donor) Exit Taine HRSA Scientific Registry of Transplant Recipients, 2022 Kidney procedure https://www.youtube.com/watch?v=zPXphpl7gco  Kidney and exercise Pre-operation and long-term rehabilitation is crucial in enhancing physical activity in kidney transplantation patients. (Case study, Yamaguchi et al, 2024)  Kidney transplant rehab Living Donor Maintenance and improvement of bed mobility, transfers and ambulation Preparation for discharge to home Wound care Recipient Maintenance and improvement of bed mobility, transfers and ambulation General strengthening as necessary (Proximal) musculature Wound care muscatel Instruction in HEP why Family education Evaluation and preparation for discharge destination  Pancreas transplant he'll ask Indications Some shit Pancreatic cancer rare- generally treated with pancreaticoduodenectomy (a.k.a. Whipple procedure- removal of the pancreas, duodenum, gallbladder, and bile duct) Diabetes (Type I and Type II) Incidence on the decline 918 in 2022, down from 963 the year prior Most are the result of damaged kidneys due to DM and included in Kidney/pancreas double organ transplant 1,486 on transplant waiting list (2022) 5 year survival rate Without transplant- 13% With transplant- 80-94% (higher based on if multiple organ transplant) Pancreas transplant procedure https://www.youtube.com/watch?v=OxxUAx0Xd6o Pancreas No specific studies were found reporting rehabilitation efficacy following pancreas transplant.  Pancreas transplant rehab Recipient Maintenance and improvement of bed mobility, transfers and ambulation General strengthening as necessary (Where?) Wound care Pinialuture Instruction in HEP Family education Evaluation and preparation for discharge destination  General Exercise/Rehabilitation after SOT control Pre-transplant Ionized Profess There was a lack of significant findings among most randomized controlled trials. (Pesce de Souza et al; 2020) Exercise training is acceptable and safe for selective SOT candidates. (Pesce de Souza et al; 2020) The effects of exercise training on exercise capacity and quality of life in SOT candidates are unclear. (Pesce de Souza et al; 2020)  Exercise Post-transplant There were no specific components of the rehabilitation program usually adjusted by patient diagnosis, or by type of organ transplanted. (Patcai et al; 2013) 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. (van Adrichem et al; 2018) Post-exercise is suggested in moderation with attention to with avoid overtraining system specific concerns POSSIBLE: MS- overuse injuries; Immun- infection; CV- events following surpassing “optimal dose of exercise”; GI- distress diarrhea, nausea, etc.; Endocrine- acute dysregulation of glucose levels; Renal- Rhabdomyolysis; Psych-  Exercise programs of combined aerobic and strength training of at least 3 months’ duration seem to be most effective at reducing BP. (Heale et al; 2017) Both aerobic and combined resistance and aerobic training programs of at least 12 weeks’ duration are effective in increasing lean muscle mass; however, there are few improvements seen in fat mass and overall body weight and BMI. (Heale et al; 2017) Interventions comprising of aerobic or combined aerobic and resistance exercise have consistently been shown to improve workload and muscle strength. Durations of between 3-12 months and both home-based and supervised training have been effective in all types of transplant recipients. (Heale et al; 2017)  Despite the evidence showing the potential benefits of physical exercise for both pre and post-SOT patients, there is a great lack of places that offer this care globally. (Nery; 2022) Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. (Bishop; 2024) There were statistically significant improvements in all outcomes after the intervention. (de Paiva Azevedo; 2023) *****Protect the patient in your care! https://painterfirm.com/medmal/Falls- during-physical-therapy-can-mean-medical-malpractice/  Treatment Take Aways for SOT SOT numbers are growing in almost all areas and will continue to grow Pre-conditioning is helpful if available Falls mean liability Exercise is safe following most SOT Acute Sub-acute Long-term ALWAYS adjusting for the patient you are caring for  Go over this slide Again Should our assessment be “different” for each of these patients? What are the significant factors we need to evaluate when working with these patients? Treating patients after transplant isn’t all that scary!  References Pesce de Souza F, Massierer D, Anand Raje U, Tansey CM, Boruff J, Janaudis-Ferreira T. Exercise interventions in solid organ transplant candidates: A systematic review. Clin Transplan et al. t. 2020;34:e13900. Patcai, J. , Disotto-Monastero, M. , Gomez, M. and Adcock, L. (2013) Inpatient rehabilitation outcomes in solid organ transplantation: Results of a unique partnership between the rehabilitation hospital and the multi-organ transplant unit in an acute hospital. Open Journal of Therapy and Rehabilitation, 1, 52-61. van Adrichem EJ, Dekker R, Krijnen WP, Verschuuren EAM, Dijkstra PU, van der Schans CP. Physical activity, sedentary time, and associated factors in recipients of solid-organ transplantation. Phys Ther. 2018;98:646–657. Heale J, Smith AC, Bishop NCEffects of Exercise and Sport in Solid Organ Transplant Recipients A Review. Am J Phys Med Rehabil 2017;96:273–88. Nery RMExercise-Based Rehabilitation for Pre- and Post-Solid Organ Transplant Patients Arq Bras Cardiol. 2022; 119(2):255-6. Bishop NC. Physical exercise, the immune system and infection risk: implications for prehabilitation and rehabilitation for solid organ transplantation candidates and recipients. Curr Opin Organ Transplant 2024, 29:271–276. Yamaguchi et al. Effectiveness of physical therapy on physical activity and employment status in kidney transplant recipients in their sixties: a case report with literature review Renal Replacement Therapy 2024;10:22. Santa Mina D et al. The role of acute in-patient rehabilitation on short-term outcomes after liver transplantation: A systematic review of the literature and expert panel recommendations. Clinical Transplantation. 2022;36:e14706. Vinaixa et al. The role of prehabilitation on short-term outcomes after liver transplantation: A review of the literature and expert panel recommendations Clinical Transplantation. 2022;36:e1468r6. de Paiva Azevedo et al. Changes in Functional Outcomes After an Inpatient Rehabilitation Program for Solid- Organ Transplant Recipients. Progress in Transplantation. 2023, Vol. 33(3) 201-207. Lv H. Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure. Liver Research 2022(6);121e129. Ursic-Bedoya J et al. Liver transplantation for alcoholic liver disease: lessonslearned and unresolved issues. World J Gastroenterol 2015 October 21; 21(39): 10994-11002  Pérez-Amate È, Roqué-Figuls M, Fernández-González M et al. Exercise interventions for adults after liver transplantation. Cochrane Database of Systematic Reviews 2023, Issue 5. Art. No.: CD013204 Yüksel Ergene T, Karadibak D, Dönmez R, Polat KY. Effects of early resistance training after liver transplantation procedures: A randomized controlled pilot trial. Turk J Gastroenterol. 2022;33(10):852-861.